Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 39.089
Filter
1.
Nat Commun ; 15(1): 3771, 2024 May 04.
Article in English | MEDLINE | ID: mdl-38704377

ABSTRACT

Ovarian metastasis is one of the major causes of treatment failure in patients with gastric cancer (GC). However, the genomic characteristics of ovarian metastasis in GC remain poorly understood. In this study, we enroll 74 GC patients with ovarian metastasis, with 64 having matched primary and metastatic samples. Here, we show a characterization of the mutation landscape of this disease, alongside an investigation into the molecular heterogeneity and pathway mutation enrichments between synchronous and metachronous metastasis. We classify patients into distinct clonal evolution patterns based on the distribution of mutations in paired samples. Notably, the parallel evolution group exhibits the most favorable prognosis. Additionally, by analyzing the differential response to chemotherapy, we identify potential biomarkers, including SALL4, CCDC105, and CLDN18, for predicting the efficacy of paclitaxel treatment. Furthermore, we validate that CLDN18 fusion mutations improve tumor response to paclitaxel treatment in GC with ovarian metastasis in vitro and vivo.


Subject(s)
Biomarkers, Tumor , Mutation , Ovarian Neoplasms , Paclitaxel , Stomach Neoplasms , Paclitaxel/therapeutic use , Humans , Stomach Neoplasms/genetics , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , Female , Ovarian Neoplasms/genetics , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/pathology , Biomarkers, Tumor/genetics , Claudins/genetics , Claudins/metabolism , Evolution, Molecular , Animals , Middle Aged , Prognosis , Cell Line, Tumor , Mice , Transcription Factors/genetics , Transcription Factors/metabolism , Aged , Antineoplastic Agents, Phytogenic/therapeutic use
2.
Cell Biochem Funct ; 42(4): e4027, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38715184

ABSTRACT

Bioactive phytocompounds are crucial components in all plants. Since the time of traditional medicine, the utilization of plants has been grounded in the potential of these bioactive compounds to treat or manage specific illnesses. These natural bioactive compounds have sparked growing interest in employing medicinal plants for addressing various conditions, such as inflammatory diseases, diabetes, and cancer. This study focuses on assessing the qualitative phytochemical composition, antioxidant potential, and cytotoxic effects of blueberry (Vaccinium sect. Cyanococcus) extract using three different solvents, namely water, ethanol, and methanol. The extract exhibited notable antioxidant activities, as evidenced by DPPH and H2O2 free radical scavenging assays. The cell viability assay also demonstrated cell growth inhibition in A549 cells. Furthermore, nine specific phytocompounds sourced from existing literature were selected for molecular docking studies against CDK6 and, AMPK key protein kinases which enhance the cancer progression. The molecular docking results also revealed favorable binding scores, with a high score of -9.5 kcal/mol in CDK6 protein and a maximum score of AMPK with targets of -8.8 kcal/mol. The selected phytocompounds' pharmacodynamic properties such as ADMET also supported the study. Furthermore, rutin stated that pre-dominantly present in blueberry plants shows a potent cytotoxicity effect in A549 cells. Functional annotations by bioinformatic analysis for rutin also revealed the strong enrichment in the involvement of PI3K/AKT1/STAT, and p53 signaling pathways. Based on this analysis, the identified rutin and other compounds hold a promising anticancer activity. Overall, the comprehensive evaluation of both in vitro and in silico data suggests that the Vaccinium sect. Cyanococcus extract could serve as a valuable source of pharmaceutical agents and may prove effective in future therapeutic applications.


Subject(s)
Blueberry Plants , Cell Proliferation , ErbB Receptors , Oxidative Stress , Plant Extracts , STAT3 Transcription Factor , Signal Transduction , Tumor Suppressor Protein p53 , Humans , Plant Extracts/pharmacology , Plant Extracts/chemistry , Blueberry Plants/chemistry , Oxidative Stress/drug effects , STAT3 Transcription Factor/metabolism , Tumor Suppressor Protein p53/metabolism , A549 Cells , Signal Transduction/drug effects , Cell Proliferation/drug effects , ErbB Receptors/metabolism , Interleukin-6/metabolism , Molecular Docking Simulation , Lung Neoplasms/metabolism , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Cell Survival/drug effects , Antioxidants/pharmacology , Antioxidants/chemistry , Antioxidants/metabolism , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Drug Screening Assays, Antitumor
3.
Med Oncol ; 41(6): 144, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38717574

ABSTRACT

Peganum harmala has been extensively employed in Algerian traditional medicine practices. This study aimed to explore the impact of n-butanol (n-BuOH) extract sourced from Peganum harmala seeds on cell proliferation, cell migration, and angiogenesis inhibition. Cytotoxic potential of n-BuOH extract was evaluated using MTT (3-(4,5-dimethylthiazol-2-yl) 2,5 diphenyltetrazolium bromide) assay against human breast adenocarcinoma MCF-7 cells, cell migration was determined using scratch assay, and anti-angiogenic effect was evaluated through macroscopic and histological examinations conducted on chick embryo chorioallantoic membrane. Additionally, this research estimated the phytochemical profile of n-BuOH extract. Fifteen phenolic compounds were identified using Ultra-performance liquid chromatography UPLC-ESI-MS-MS analysis. In addition, the n-BuOH extract of P. harmala exhibited potent antioxidant and free radical scavenging properties. The n-BuOH extract showed potent cytotoxicity against MCF-7 cell with an IC50 value of 8.68 ± 1.58 µg/mL. Furthermore, n-BuOH extract significantly reduced migration. A strong anti-angiogenic activity was observed in the groups treated with n-BuOH extract in comparison to the negative control. Histological analysis confirmed the anti-angiogenic effect of the n-BuOH extract. This activity is probably a result of the synergistic effects produced by different polyphenolic classes.


Subject(s)
Angiogenesis Inhibitors , Cell Movement , Peganum , Phenols , Plant Extracts , Humans , Cell Movement/drug effects , Plant Extracts/pharmacology , Plant Extracts/chemistry , Peganum/chemistry , Chick Embryo , Phenols/pharmacology , Phenols/analysis , Angiogenesis Inhibitors/pharmacology , MCF-7 Cells , Animals , Cell Proliferation/drug effects , Phytochemicals/pharmacology , Phytochemicals/chemistry , Antioxidants/pharmacology , Antioxidants/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Chorioallantoic Membrane/drug effects , Chorioallantoic Membrane/blood supply
4.
Med Oncol ; 41(6): 143, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38717628

ABSTRACT

Picrorhiza kurroa, an "Indian gentian," a known Himalayan medicinal herb with rich source of phytochemicals like picrosides I, II, and other glycosides, has been traditionally used for the treatment of liver and respiratory ailments. Picrosides anti-proliferative, anti-oxidant, anti-inflammatory and other pharmacological properties were evaluated in treating triple-negative breast cancer (TNBC). Picroside I and II were procured from Sigma-Aldrich and were analyzed for anti-cancer activity in triple-negative breast cancer (MDA-MB-231) cells. Cell viability was analyzed using MTT and trypan blue assays. Apoptosis was analyzed through DNA fragmentation and Annexin V/PI flow cytometric analysis. Wound healing and cell survival assays were employed to determine the inhibition of invasion capacity and anti-proliferative activity of picrosides in MDA-MB-231 cells. Measurement of intracellular ROS was studied through mitochondrial membrane potential assessment using DiOC6 staining for anti-oxidant activity of picrosides in MDA-MB-231 cells. Both Picroside I and II have shown decreased cell viability of MDA-MB-231 cells with increasing concentrations. IC50 values of 95.3 µM and 130.8 µM have been obtained for Picroside I and II in MDA-MB-231 cells. Early apoptotic phase have shown an increase of 20% (p < 0.05) with increasing concentrations (0, 50, 75, and 100 µM) of Picroside I and 15% (p < 0.05) increase with Picroside II. Decrease in mitochondrial membrane potential of 2-2.5-fold (p < 0.05) was observed which indicated decreased reactive oxygen species (ROS) generation with increasing concentrations of Picroside I and II. An increasing percentage of 70-80% (p < 0.05) cell population was arrested in G0/G1 phase of cell cycle after Picroside I and II treatment in cancer cells. Our results suggest that Picroside I and II possess significant anti-proliferative and anti-cancer activity which is mediated by inhibition of cell growth, decreased mitochondrial membrane potential, DNA damage, apoptosis, and cell cycle arrest. Therefore, Picroside I and II can be developed as a potential anti-cancer drug of future and further mechanistic studies are underway to identify the mechanism of anti-cancer potential.


Subject(s)
Apoptosis , Cell Proliferation , Cinnamates , Iridoid Glucosides , Membrane Potential, Mitochondrial , Reactive Oxygen Species , Triple Negative Breast Neoplasms , Humans , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/pathology , Triple Negative Breast Neoplasms/metabolism , Cell Proliferation/drug effects , Cell Line, Tumor , Apoptosis/drug effects , Iridoid Glucosides/pharmacology , Reactive Oxygen Species/metabolism , Female , Membrane Potential, Mitochondrial/drug effects , Cinnamates/pharmacology , Cell Survival/drug effects , Antineoplastic Agents, Phytogenic/pharmacology
5.
Balkan Med J ; 41(3): 193-205, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38700358

ABSTRACT

Background: Paclitaxel (PAX) is a widely used chemotherapy drug for various cancer types but often induces significant toxicity in multiple organ systems. Silymarin (SIL), a natural flavonoid, has shown therapeutic potential due to its multiple benefits. Aims: To evaluate the therapeutic efficacy of SIL in mitigating liver and kidney damage induced by PAX in rats, focusing on oxidative stress, inflammation, and apoptosis pathways. Study Design: Experimental animal model. Methods: The study included 28 male Wistar rats aged 12-14 weeks weighing 270-300 g. The rats were divided into four groups: control, SIL, PAX, and PAX + SIL, with seven in each group. The rats received intraperitoneal (i.p.) injections at a dose of 2 mg per kilogram of body weight of PAX for 5 successive days, followed by oral gavage with 200 mg/kg body mass of SIL for 10 uninterrupted days. We examined the effect of SIL on specific serum biochemical parameters using an autoanalyzer and rat-specific kits. The spectrophotometric methods was used to investigate oxidative stress indicators in kidney and liver tissues. Aquaporin-2 (AQP-2), B-cell lymphoma-2 (Bcl-2), cysteine aspartate-specific protease-3 (caspase-3), interleukin-6 (IL-6), nuclear factor kappa B (NF-κB), and streptavidin-biotin staining were used to assess immunoreactivity in PAX-induced liver and kidney injury models. Results: SIL treatment significantly reduced serum levels of alanine aminotransferase, aspartate aminotransferase, creatinine, urea, and C-reactive protein, indicating its effectiveness in treating PAX-induced liver and kidney injury. SIL treatment significantly reduced oxidative stress by increasing essential antioxidant parameters, such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione. It also reduced malondialdehyde levels in liver and kidney tissues of SIL-PAX groups (p < 0.05). SIL administration reduced NF-κB, caspase-3, and IL-6 expression while increasing Bcl-2 and AQP2 levels in liver and kidney tissues of rats treated with SIL and PAX (p < 0.05). Conclusion: Our findings indicate the potential of SIL to alleviate PAX-induced liver and kidney damage in rats by reducing oxidative stress, inflammation, and apoptotic processes.


Subject(s)
Apoptosis , Inflammation , Oxidative Stress , Paclitaxel , Rats, Wistar , Silymarin , Animals , Oxidative Stress/drug effects , Rats , Male , Apoptosis/drug effects , Inflammation/drug therapy , Paclitaxel/pharmacology , Paclitaxel/therapeutic use , Silymarin/pharmacology , Silymarin/therapeutic use , Chemical and Drug Induced Liver Injury/prevention & control , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/etiology , Antioxidants/pharmacology , Antioxidants/therapeutic use , Liver/drug effects , Kidney/drug effects , Antineoplastic Agents, Phytogenic/therapeutic use , Antineoplastic Agents, Phytogenic/pharmacology
6.
Curr Pharm Biotechnol ; 25(5): 599-622, 2024.
Article in English | MEDLINE | ID: mdl-38807329

ABSTRACT

Colorectal cancer (CRC) is a complex and multifactorial disorder in middle-aged people. Several modern medicines are available for treating and preventing it. However, their therapeutic uses are limited due to drawbacks, such as gastric perforation, diarrhea, intestinal bleeding, abdominal cramps, hair loss, nausea, vomiting, weight loss, and adverse reactions. Hence, there is a continuous quest for safe and effective medicines to manage human health problems, like CRC. In this context, herbal medicines are considered an alternative disease control system. It has become popular in countries, like American, European, and Asian, due to its safety and effectiveness, which has been practiced for 1000 years. During the last few decades, herbal medicines have been widely explored through multidisciplinary fields for getting active compounds against human diseases. Several herbal bioactives, like curcumin, glycyrrhizin, paclitaxel, chlorogenic acid, gallic acid, catechin, berberine, ursolic acid, betulinic acid, chrysin, resveratrol, quercetin, etc., have been found to be effective against CRC. However, their pharmacological applications are limited due to low bioavailability and therapeutic efficacy apart from their several health benefits. An effective delivery system is required to increase their bioavailability and efficacy. Therefore, targeted novel drug delivery approaches are promising for improving these substances' solubility, bioavailability, and therapeutic effects. Novel carrier systems, such as liposomes, nanoparticles, micelles, microspheres, dendrimers, microbeads, and hydrogels, are promising for delivering poorly soluble drugs to the target site, i.e., the colon. Thus, the present review is focused on the pathophysiology, molecular pathways, and diagnostic and treatment approaches for CRC. Moreover, an emphasis has been laid especially on herbal bioactive-based novel delivery systems and their clinical updates.


Subject(s)
Colorectal Neoplasms , Humans , Colorectal Neoplasms/drug therapy , Drug Carriers/chemistry , Animals , Nanoparticles/chemistry , Drug Delivery Systems/methods , Phytochemicals/therapeutic use , Phytochemicals/chemistry , Phytochemicals/administration & dosage , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/therapeutic use , Antineoplastic Agents, Phytogenic/chemistry
7.
Drug Des Devel Ther ; 18: 1673-1694, 2024.
Article in English | MEDLINE | ID: mdl-38779590

ABSTRACT

Pristimerin, a natural triterpenoid isolated from the plants of southern snake vine and Maidenwood in the family Weseraceae, is anti-inflammatory, insecticidal, antibacterial, and antiviral substance and has been used for its cardioprotective and antitumor effects and in osteoporosis treatment. These qualities explain Pristimerin's therapeutic effects on different types of tumors and other diseases. More and more studies have shown that pristimerin acts in a wide range of biological activities and has shown great potential in various fields of modern and Chinese medicine. While Pristimerin's wide range of pharmacological effects have been widely studied by others, our comprehensive review suggests that its mechanism of action may be through affecting fundamental cellular events, including blocking the cell cycle, inducing apoptosis and autophagy, and inhibiting cell migration and invasion, or through activating or inhibiting certain key molecules in several cell signaling pathways, including nuclear factor κB (NF-κB), phosphatidylinositol 3-kinase/protein kinase B/mammalian-targeted macromycin (PI3K/Akt/mTOR), mitogen-activated protein kinases (MAPKs), extracellular signal-regulated protein kinase 1/2 (ERK1/2), Jun amino-terminal kinase (JNK1/2/3), reactive oxygen species (ROS), wingless/integrin1 (Wnt)/ß-catenin, and other signaling pathways. This paper reviews the research progress of Pristimerin's pharmacological mechanism of action in recent years to provide a theoretical basis for the molecular targeting therapy and further development and utilization of Pristimerin. It also provides insights into improved treatments and therapies for clinical patients and the need to explore pristimerin as a potential facet of treatment.


Subject(s)
Pentacyclic Triterpenes , Signal Transduction , Animals , Humans , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Apoptosis/drug effects , Pentacyclic Triterpenes/pharmacology , Signal Transduction/drug effects , Triterpenes/pharmacology , Triterpenes/chemistry , Triterpenes/isolation & purification
8.
Sheng Wu Gong Cheng Xue Bao ; 40(5): 1380-1405, 2024 May 25.
Article in Chinese | MEDLINE | ID: mdl-38783804

ABSTRACT

Paclitaxel, a rare diterpene extracted from the bark of Chinese yew (Taxus chinensis), is renowned for its anti-cancer activity and serves as a primary drug for treating cancers. Due to the exceptionally low content of paclitaxel in the bark, a semi-synthetic method that depletes Chinese yew resources is used in the production of paclitaxel, which, however, fails to meet the escalating clinical demand. In recent years, researchers have achieved significant progress in heterologous biosynthesis and metabolic engineering for the production of paclitaxel. This article comprehensively reviews the advancements in paclitaxel production, encompassing chemical synthesis, heterologous biosynthesis, and cell engineering. It provides an in-depth introduction to the biosynthetic pathway and transcriptional regulation mechanisms of paclitaxel, aiming to provide a valuable reference for further research on paclitaxel biosynthesis.


Subject(s)
Paclitaxel , Paclitaxel/biosynthesis , Metabolic Engineering/methods , Taxus/genetics , Taxus/metabolism , Antineoplastic Agents, Phytogenic/biosynthesis , Antineoplastic Agents, Phytogenic/pharmacology , Transcription, Genetic , Biosynthetic Pathways/genetics
9.
FASEB J ; 38(10): e23689, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38785406

ABSTRACT

Neuroblastoma, a prevalent extracranial solid tumor in children, arises from undifferentiated nerve cells. While tumor vasculature, often characterized by increased permeability, influences metastasis and recurrence, the direct impact of blood-borne molecules on tumor progression remains unclear. In the present study, we focused on the effect of exposure to albumin, one of the most abundant proteins in the serum, on human neuroblastoma cells. Albumin exposure elevated oxidative stress and led to mitochondria dysfunction via the activation of TGFß and PI3K pathways, accompanied by an increase in the metastatic and invasive properties of neuroblastoma cells. Proteins relevant to the induction of autophagy were upregulated in response to prolonged albumin exposure. Additionally, pre-exposure to albumin before treatment resulted in increased resistance to paclitaxel. Two valeriana-type iridoid glycosides, patrisophoroside and patrinalloside, recently isolated from Nardostachys jatamansi significantly mitigated the effect of albumin on oxidative stress, cell invasiveness, and chemoresistance. These findings illuminate the potential role of blood-borne molecules, such as albumin, in the progression and metastasis of neuroblastoma, as well as the possible therapeutic implications of valeriana-type iridoid glycosides in anti-cancer treatment.


Subject(s)
Drug Resistance, Neoplasm , Iridoid Glycosides , Neuroblastoma , Paclitaxel , Humans , Neuroblastoma/pathology , Neuroblastoma/metabolism , Neuroblastoma/drug therapy , Drug Resistance, Neoplasm/drug effects , Paclitaxel/pharmacology , Iridoid Glycosides/pharmacology , Cell Line, Tumor , Neoplasm Invasiveness , Oxidative Stress/drug effects , Antineoplastic Agents, Phytogenic/pharmacology , Valerian/chemistry , Serum Albumin/metabolism
10.
J Biochem Mol Toxicol ; 38(6): e23735, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38773908

ABSTRACT

Cancer is one of the major causes of death worldwide, with more than 10 million deaths annually. Despite tremendous advances in the health sciences, cancer continues to be a substantial global contributor to mortality. The current treatment methods demand a paradigm shift that not only improves therapeutic efficacy but also minimizes the side effects of conventional medications. Recently, an increased interest in the potential of natural bioactive compounds in the treatment of several types of cancer has been observed. Ononin, also referred to as formononetin-7-O-ß-d-glucoside, is a natural isoflavone glycoside, derived from the roots, stems, and rhizomes of various plants. It exhibits a variety of pharmacological effects, including Antiangiogenic, anti-inflammatory, antiproliferative, proapoptotic, and antimetastatic activities. The current review presents a thorough overview of sources, chemistry, pharmacokinetics, and the role of ononin in affecting various mechanisms involved in cancer. The review also discusses potential synergistic interactions with other compounds and therapies. The combined synergistic effect of ononin with other compounds increased the efficacy of treatment methods. Finally, the safety studies, comprising both in vitro and in vivo assessments of ononin's anticancer activities, are described.


Subject(s)
Isoflavones , Neoplasms , Isoflavones/pharmacology , Isoflavones/chemistry , Isoflavones/therapeutic use , Humans , Animals , Neoplasms/drug therapy , Neoplasms/metabolism , Neoplasms/pathology , Glucosides/pharmacology , Glucosides/therapeutic use , Glucosides/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/therapeutic use , Glycosides/pharmacology , Glycosides/therapeutic use , Glycosides/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/chemistry
11.
BMC Cancer ; 24(1): 566, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38711004

ABSTRACT

BACKGROUND: Resveratrol has demonstrated its ability to regulate BRCA1 gene expression in breast cancer cells, and previous studies have established the binding of MBD proteins to BRCA1 gene promoter regions. However, the molecular mechanism underlying these interactions remains to be elucidated. The aimed to evaluate the impact of MBD proteins on the regulation of BRCA1, BRCA2, and p16 genes and their consequential effects on breast cancer cells. METHODS: Efficacy of resveratrol was assessed using the MTT assay. Binding interactions were investigated through EMSA, ChIP, & MeIP assay. Expression analyses of MBD genes and proteins were conducted using qRT-PCR and western blotting, respectively. Functional assays, including clonogenic, migratory, and sphere formation assays were used to assess cancer cells' colony-forming, metastatic, and tumor-forming abilities. The cytotoxicity of resveratrol on cancer cells was also tested using an apoptosis assay. RESULTS: The study determined an IC50 of 30µM for resveratrol. MBD proteins were found to bind to the BRCA1 gene promoter. Resveratrol exhibited regulatory effects on MBD gene expression, subsequently impacting BRCA1 gene expression and protein levels. Higher concentrations of resveratrol resulted in reduced colony and sphere formation, decreases migration of cancer cells, and an increases number of apoptotic cells in breast cancer cells. Impact Identification of MBD2-BRCA1 axis indicates their significant role in the induction of apoptosis and reduction of metastasis and proliferation in breast cancer cells. Further therapy can be designed to target these MBD proteins and resveratrol could be used along with other anticancer drugs to target breast cancer. CONCLUSIONS: In conclusion MBD2 protein interact to the BRCA1 gene promoter, and resveratrol modulates MBD2 gene expression, which in turn regulates BRCA1 gene expression, and inhibits cell proliferation, migration, and induces apoptosis in ER+, PR+ & Triple negative breast cancer cells.


Subject(s)
BRCA1 Protein , DNA-Binding Proteins , Gene Expression Regulation, Neoplastic , Promoter Regions, Genetic , Resveratrol , Triple Negative Breast Neoplasms , Resveratrol/pharmacology , Resveratrol/therapeutic use , Humans , BRCA1 Protein/genetics , BRCA1 Protein/metabolism , Female , Gene Expression Regulation, Neoplastic/drug effects , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/pathology , Triple Negative Breast Neoplasms/metabolism , DNA-Binding Proteins/metabolism , DNA-Binding Proteins/genetics , Cell Line, Tumor , Apoptosis/drug effects , Cell Proliferation/drug effects , Cell Movement/drug effects , Receptors, Estrogen/metabolism , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/therapeutic use
12.
Org Lett ; 26(20): 4302-4307, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38728049

ABSTRACT

A plant used in an Indonesian traditional herbal medicine as a diabetes treatment and known locally as "Jampu Salo" was collected on Sulawesi Island, Indonesia. It was identified as Syzygium oblanceolatum (C. B. Rob.) Merr. (Myrtaceae) and found for the first time in Sulawesi; it was previously reported only in the eastern Philippines and Borneo. A phytochemical study of S. oblanceolatum led to the isolation of three unprecedented meroterpenoids, syzygioblanes A-C (1-3, respectively). These compounds might be biosynthesized through [4+2] cycloaddition of various germacrane-based cyclic sesquiterpenoids with the flavone desmethoxymatteucinol to form a spiro skeleton. The unique and complex structures were elucidated by microcrystal electron diffraction analysis in addition to general analytical techniques such as high-resolution mass spectrometry, various nuclear magnetic resonance methods, and infrared spectroscopy. Synchrotron X-ray diffraction and calculations of electronic circular dichroism spectra helped to determine the absolute configurations. The newly isolated compounds exhibited collateral sensitivity to more strongly inhibit the growth of a multidrug resistant tumor cell line compared to a chemosensitive tumor cell line.


Subject(s)
Sesquiterpenes , Syzygium , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacology , Sesquiterpenes/isolation & purification , Syzygium/chemistry , Molecular Structure , Indonesia , Humans , Flavanones/chemistry , Flavanones/pharmacology , Flavanones/isolation & purification , Medicine, Traditional , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Drug Screening Assays, Antitumor , Cell Line, Tumor
13.
Yakugaku Zasshi ; 144(5): 553-565, 2024.
Article in Japanese | MEDLINE | ID: mdl-38692932

ABSTRACT

A series of antitumor bicyclic hexapeptide RA-VII analogues modified at residue 2, 3, or 6 were prepared by the chemical transformation of the hydroxy, methoxy, or carboxy groups or the aromatic rings of natural peptides RA-II, III, V, VII, and X. Analogues with modified side chains or peptide backbones, which cannot be prepared by the chemical transformation of their natural peptides, and newly isolated peptides from Rubia cordifolia roots were synthesized by using protected cycloisodityrosines prepared by the degradation of bis(thioamide) obtained from RA-VII or the diphenyl ether formation of boronodipeptide under the modified Chan-Lam coupling reaction conditions. Studies of the conformational features of the analogues and the newly isolated peptides and their relationships with cytotoxic activities against the HCT-116, HL-60, KATO-III, KB, L1210, MCF-7, and P-388 cell lines revealed the following: the methoxy group at residue 3 is essential for the potent cytotoxic activity; the methyl group at Ala-2 and Ala-4 but not at D-Ala-1 is required to establish the bioactive conformation; the N-methyl group at Tyr-5 is necessary for the peptides to adopt the active conformation preferentially; and the orientation of Tyr-5 and/or Tyr-6 phenyl rings has a significant effect on the cytotoxic activity.


Subject(s)
Peptides, Cyclic , Humans , Structure-Activity Relationship , Peptides, Cyclic/chemistry , Peptides, Cyclic/pharmacology , Peptides, Cyclic/chemical synthesis , Oligopeptides/chemistry , Oligopeptides/pharmacology , Oligopeptides/chemical synthesis , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Rubia/chemistry , Plant Roots/chemistry , Cell Line, Tumor , Antineoplastic Agents, Phytogenic/pharmacology , Protein Conformation
14.
J Evid Based Integr Med ; 29: 2515690X241251558, 2024.
Article in English | MEDLINE | ID: mdl-38689490

ABSTRACT

Liver cancer is the most common cancer among males in Africa. The disease has a poor prognosis and its treatment is associated with toxicity and resistance. For this reason, numerous herbal combinations are being subjected to anticancer screening to circumvent the shortcomings of the conventional anticancer drugs. In the current study, the in vivo anti-cancer effects of the chloroform root extract of the herb, Clausena excavata Burm were investigated. Liver cancer was induced in mice by a single intraperitoneal injection of diethylnitrosamine (DEN) followed by oral administration of the promoter of carcinogenesis, 2-aminoacetyl fluorine that was mixed with the mice feed. The cytotoxicity of the root extract of C. excavata on liver cancer cells was investigated using liver enzyme, histology, DNA fragmentation and caspases assays. Real time qPCR was conducted to evaluate the effect of the extract on apoptotic genes. The findings revealed that the extract of C. excavata significantly decreased the progression of hepatocarcinogenesis and the toxicity-induced production of the liver enzymes, alanine and aspartate aminotransferases. The histological analyses of the liver tissues revealed evidence of apoptotic cell death. The extract also provoked significant (p < .05) expressions of caspase 9 protein and gene as well as other apoptotic genes (P53, P27, Apaf-1, cytochrome C, bax and bid). Therefore, we postulate that the chloroform root extract of C. excavata induces apoptosis of liver cancer in mice.


Subject(s)
Apoptosis , Carcinoma, Hepatocellular , Chloroform , Clausena , Liver Neoplasms , Plant Extracts , Plant Roots , Animals , Plant Extracts/pharmacology , Mice , Plant Roots/chemistry , Male , Liver Neoplasms/drug therapy , Clausena/chemistry , Carcinoma, Hepatocellular/drug therapy , Apoptosis/drug effects , Humans , Antineoplastic Agents, Phytogenic/pharmacology , Liver/drug effects , Liver/metabolism , Liver/pathology , Diethylnitrosamine/toxicity
15.
Med Oncol ; 41(6): 156, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38750377

ABSTRACT

This study explores the therapeutic potential of phytochemicals derived from Morus alba for colorectal cancer (CRC) treatment. Colorectal cancer is a global health concern with increasing mortality rates, necessitating innovative strategies for prevention and therapy. Employing in silico analysis, molecular docking techniques (MDT), and molecular dynamics simulations (MDS), the study investigates the interactions between Morus alba-derived phytochemicals and key proteins (AKT1, Src, STAT3, EGFR) implicated in CRC progression. ADME/T analysis screens 78 phytochemicals for drug-like and pharmacokinetic properties. The study integrates Lipinski's Rule of Five and comprehensive bioactivity assessments, providing a nuanced understanding of Morus alba phytoconstituent's potential as CRC therapeutic agents. Notably, 14 phytochemicals out of 78 emerge as potential candidates, demonstrating oral bioavailability and favorable bioactivity scores. Autodock 1.5.7 is employed for energy minimization followed by molecular docking with the highest binding energy observed to be - 11.7 kcal/mol exhibited by Kuwanon A against AKT1. Molecular dynamics simulations and trajectory path analysis were conducted between Kuwanon A and AKT1 at the Pleckstrin homology (PH) domain region (TRP80), revealing minimal deviations. In comparison to the standard drug Capivasertib, the phytochemical Kuwanon A emerges as a standout candidate based on computational analysis. This suggests its potential as an alternative to mitigate the limitations associated with the standard drug. The research aims to provide insights for future experimental validations and to stimulate the development of Kuwanon A as a novel, effective therapeutic agent for managing colorectal cancer.


Subject(s)
Colorectal Neoplasms , Molecular Docking Simulation , Molecular Dynamics Simulation , Morus , Phytochemicals , Morus/chemistry , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Colorectal Neoplasms/metabolism , Phytochemicals/chemistry , Phytochemicals/pharmacology , Phytochemicals/pharmacokinetics , Humans , Proto-Oncogene Proteins c-akt/metabolism , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/metabolism , STAT3 Transcription Factor/metabolism , Plant Extracts/chemistry , Plant Extracts/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/pharmacokinetics , Antineoplastic Agents, Phytogenic/chemistry , src-Family Kinases/metabolism
16.
Breast Dis ; 43(1): 99-110, 2024.
Article in English | MEDLINE | ID: mdl-38758988

ABSTRACT

INTRODUCTION: Indonesian civilization extensively uses traditional medicine to cure illnesses and preserve health. The lack of knowledge on the security and efficacy of medicinal plants is still a significant concern. Although the precise chemicals responsible for this impact are unknown, ginger is a common medicinal plant in Southeast Asia that may have anticancer qualities. METHOD: Using data from Dudedocking, a machine-learning model was created to predict possible breast anticancer chemicals from ginger. The model was used to forecast substances that block KIT and MAPK2 proteins, essential elements in breast cancer. RESULT: Beta-carotene, 5-Hydroxy-74'-dimethoxyflavone, [12]-Shogaol, Isogingerenone B, curcumin, Trans-[10]-Shogaol, Gingerenone A, Dihydrocurcumin, and demethoxycurcumin were all superior to the reference ligand for MAPK2, according to molecular docking studies. Lycopene, [8]-Shogaol, [6]-Shogaol, and [1]-Paradol exhibited low toxicity and no Lipinski violations, but beta carotene had toxic predictions and Lipinski violations. It was anticipated that all three substances would have anticarcinogenic qualities. CONCLUSION: Overall, this study shows the value of machine learning in drug development and offers insightful information on possible anticancer chemicals from ginger.


Subject(s)
Breast Neoplasms , Machine Learning , Molecular Docking Simulation , Zingiber officinale , Zingiber officinale/chemistry , Humans , Breast Neoplasms/drug therapy , Female , Plant Extracts/pharmacology , Computer Simulation , Antineoplastic Agents, Phytogenic/pharmacology , Catechols/pharmacology
17.
Medicine (Baltimore) ; 103(20): e38207, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38758870

ABSTRACT

This study aimed to investigate changes in hand sensation (finger tactile threshold and two-point discrimination) and function in patients with malignant lymphoma, particularly during the early stages of chemotherapy with vincristine. Eighteen patients with malignant lymphoma were enrolled in this study. Data on the Common Terminology Criteria for Adverse Events Version 4.0, the visual analog scale for hand numbness, the Semmes Weinstein monofilament test, static and moving two-point discrimination (2PD), grip strength, pinch strength, and the Purdue Pegboard test were collected at 3 time points: before the start of chemotherapy (T0), after the first cycle of chemotherapy (T1), and after the second cycle of chemotherapy (T2). No significant changes were observed in Semmes Weinstein monofilament test at T0, T1, or T2 in either hand. However, the static 2PD was significantly worse for the right ring, little, and left middle fingers, whereas the moving 2PD was significantly worse for the right ring, left index, middle, and ring fingers. Furthermore, the visual analog scale scores for hand numbness and left-hand grip strength worsened significantly. Right-hand grip strength, pinch strength of both hands, and Purdue Pegboard test showed no significant deterioration. Chemotherapy with vincristine may affect hand sensation and function in patients with malignant lymphoma by exacerbating finger 2PD and hand numbness. Additionally, during the early stages of vincristine chemotherapy, it is important to monitor for a decrease in grip strength specifically in the left hand.


Subject(s)
Hand Strength , Hand , Lymphoma , Vincristine , Humans , Vincristine/adverse effects , Vincristine/administration & dosage , Male , Female , Middle Aged , Lymphoma/drug therapy , Aged , Adult , Antineoplastic Agents, Phytogenic/adverse effects , Antineoplastic Agents, Phytogenic/administration & dosage , Hypesthesia/chemically induced
18.
Pharm Biol ; 62(1): 367-393, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38745507

ABSTRACT

CONTEXT: Rice bran arabinoxylan compound (RBAC) is a natural immunomodulator with anticancer properties. OBJECTIVE: This study critically evaluates the available evidence on the biological pathways of RBAC and its effects on cancer treatment. METHODS: This secondary analysis of a scoping review includes studies evaluating the mechanisms of RBAC on healthy or malignant cells, animal models, or humans for cancer prevention or treatment. Data from randomized controlled trials on survival and quality of life outcomes were subjectd to meta analysis. RESULTS: The evidence synthesis was based on 38 articles. RBAC exhibited antitumor properties by promoting apoptosis and restoring immune function in cancer patients to enhance inflammatory and cytotoxic responses to block tumorigenesis. RBAC works synergistically with chemotherapeutic agents by upregulating drug transport. In a clinical trial, combining RBAC with chemoembolization in treating liver cancer showed improved response, reduced recurrence rates, and prolonged survival. RBAC also augments the endogenous antioxidant system to prevent oxidative stress and protect against radiation side effects. In addition, RBAC has chemoprotective effects. Animals and humans have exhibited reduced toxicity and side effects from chemotherapy. Meta analysis indicates that RBAC treatment increases the survival odds by 4.02-times (95% CI: 1.67, 9.69) in the first year and 2.89-times (95% CI: 1.56, 5.35) in the second year. CONCLUSION: RBAC is a natural product with immense potential in cancer treatment. Additional research is needed to characterize, quantify, and standardize the active ingredients in RBAC responsible for the anticancer effects. More well-designed, large-scale clinical trials are required to substantiate the treatment efficacies further.


Subject(s)
Neoplasms , Oryza , Xylans , Xylans/pharmacology , Humans , Animals , Neoplasms/drug therapy , Biological Products/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/administration & dosage , Randomized Controlled Trials as Topic , Antineoplastic Agents/pharmacology
19.
Molecules ; 29(9)2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38731434

ABSTRACT

Cannabidiol (CBD), a non-psychoactive ingredient extracted from the hemp plant, has shown therapeutic effects in a variety of diseases, including anxiety, nervous system disorders, inflammation, and tumors. CBD can exert its antitumor effect by regulating the cell cycle, inducing tumor cell apoptosis and autophagy, and inhibiting tumor cell invasion, migration, and angiogenesis. This article reviews the proposed antitumor mechanisms of CBD, aiming to provide references for the clinical treatment of tumor diseases and the rational use of CBD.


Subject(s)
Apoptosis , Cannabidiol , Neoplasms , Cannabidiol/pharmacology , Cannabidiol/therapeutic use , Cannabidiol/chemistry , Humans , Apoptosis/drug effects , Neoplasms/drug therapy , Neoplasms/pathology , Neoplasms/metabolism , Animals , Autophagy/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Cell Movement/drug effects , Cell Cycle/drug effects , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/chemistry
20.
Molecules ; 29(9)2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38731446

ABSTRACT

Ilama leaves are an important source of secondary metabolites with promising anticancer properties. Cancer is a disease that affects a great number of people worldwide. This work aimed to investigate the in vivo, in vitro and in silico anticancer properties of three acyclic terpenoids (geranylgeraniol, phytol and farnesyl acetate) isolated from petroleum ether extract of ilama leaves. Their cytotoxic activity against U-937 cells was assessed using flow cytometry to determine the type of cell death and production of reactive oxygen species (ROS). Also, a morphological analysis of the lymph nodes and a molecular docking study using three proteins related with cancer as targets, namely, Bcl-2, Mcl-1 and VEGFR-2, were performed. The flow cytometry and histomorphological analysis revealed that geranylgeraniol, phytol and farnesyl acetate induced the death of U-937 cells by late apoptosis and necrosis. Geranylgeraniol and phytol induced a significant increase in ROS production. The molecular docking studies showed that geranylgeraniol had more affinity for Bcl-2 and VEGFR-2. In the case of farnesyl acetate, it showed the best affinity for Mcl-1. This study provides information that supports the anticancer potential of geranylgeraniol, phytol and farnesyl acetate as compounds for the treatment of cancer, particularly with the potential to treat non-Hodgkin's lymphoma.


Subject(s)
Molecular Docking Simulation , Plant Extracts , Plant Leaves , Plants, Medicinal , Reactive Oxygen Species , Humans , Plant Leaves/chemistry , Plants, Medicinal/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Reactive Oxygen Species/metabolism , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Mexico , Apoptosis/drug effects , Cell Line, Tumor , Animals , Vascular Endothelial Growth Factor Receptor-2/metabolism , Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors , Computer Simulation , Proto-Oncogene Proteins c-bcl-2/metabolism , U937 Cells
SELECTION OF CITATIONS
SEARCH DETAIL
...