Cratoxylum formosum ssp. pruniflorum induces gastric cancer cell apoptosis and pyroptosis through the elevation of ROS and cell cycle arrest.

Cratoxylum formosum ssp. pruniflorum (CF), a traditional medicinal plant in Southern China, is widely recognized as a popular medicinal and tea plant traditionally utilized by diverse linguistic groups in the region for the treatment of gastrointestinal ailments. The objective of this study was to explore the active components and mechanisms of CF against gastric cancer (GC). The chemical ingredients of CF were obtained by using UPLC-MS/MS-based metabolomics. MGC-803 and HGC-27 cells were employed to investigate the direct anti-GC effect. The potential targets and signaling pathway of CF were identified through network pharmacology and proteomics, followed by subsequent experimental validation. Through UPLC-MS/MS metabolomics analysis, a total of 197 chemical ingredients were identified in CF leaves. Network pharmacology and proteomics techniques revealed 25 potential targets for GC, with a protein-protein interaction (PPI) network highlighting 12 cores targets, including CTNNB1, CDK2, et al. Furthermore, seven key CF ingredients - vismione B, feruloylcholine, α-amyrin, vanillic acid, galangin, cinnamic acid, and caffeic acid - were found to mediate anti-GC effects through pathways such as reactive oxygen species (ROS) and cell cycle signaling pathway. In vitro experiments demonstrated that CF significantly inhibited the proliferation and migration of GC cells, increased intracellular reactive oxygen species (ROS), malondialdehyde (MDA) and lactate dehydrogenase (LDH) levels, arrested the cell cycle at the S-phase, induced apoptosis and pyroptosis, and upregulated expression of apoptosis proteins (Bax, Bax/Bcl-2, cleaved-Caspase-3/Caspase-3), and pyroptosis proteins (GSDMD-N/GSDMD and GSDME-N/GSDME), while downregulating expression of cell cycle proteins (CDK2 and cyclin A1) as well as necroptosis proteins (RIP1 and MLKL). Collectively, these findings reveal CF's therapeutic potential against GC by the augmentation of ROS production, cell cycle arrest, promotion of apoptosis, and pyroptosis, offering valuable evidence for the development and utilization of CF in clinical settings.

Extraction and Isolation of Two Polysaccharides from Chloranthus japonicus Sieb. and Evaluation of Their Anti-Gastric Cancer Activities.

Two unreported heteropolysaccharides, denoted as YCJP-1 and YCJP-2, were isolated from the herbs of Chloranthus japonicus. YCJP-1 was a heteropolysaccharide composed of glucose, galactose, arabinose, mannose, rhamnose, and a minor proportion of uronic acids, with the molecular weight mainly distributed in the 74,475-228,443 Da range. YCJP-2 was mainly composed of glucose, mannose, and galactose, with the molecular weights ranging from 848 to 5810 Da. To further evaluate the anti-gastric cancer effects of C. japonicus, the inhibitory effects of the crude polysaccharide (YCJP) and the purified polysaccharides (YCJP-1 and YCJP-2) were determined using a CCK-8 assay and colon-forming assay on MGC-803 and AGS gastric cancer cell lines. Our results showed that YCJP, YCJP-1, and YCJP-2 possess prominent inhibitory effects on the proliferation of MGC-803 and AGS cells, and the AGS cell was more sensitive to YCJP, YCJP-1, and YCJP-2. Moreover, YCJP-2 demonstrated superior anti-gastric cancer effects compared to YCJP-1. This could potentially be attributed to YCJP-2's higher glucose content and narrower molecular weight distribution.

Experimental and computational study on anti-gastric cancer activity and mechanism of evodiamine derivatives.

Introduction: Human topoisomerase 1 (TOP1) is an important target of various anticancer compounds. The design and discovery of inhibitors targeting TOP1 are of great significance for the development of anticancer drugs. Evodiamine and thieno [2,3-d] pyridine hybrids show potential antitumor activity. Herein, the anti-gastric cancer activities of these hybrids were investigated. Methods: The inhibitory effects of different concentrations of ten evodiamine derivatives on the gastric cancer cell line SGC-7901 were assessed using a methyl thiazolyl tetrazolium assay. Compounds EVO-1 and EVO-6 strongly inhibited gastric cancer cell proliferation, with inhibition rates of 81.17% ± 5.08% and 80.92% ± 2.75%, respectively. To discover the relationship between the structure and activity of these two derivatives, density functional theory was used to investigate their optimized geometries, natural population charges, frontier molecular orbitals, and molecular electrostatic potentials. To clarify their anti-gastric cancer mechanisms, molecular docking, molecular dynamics simulations, and binding free energy calculations were performed against TOP1. Results: The results demonstrated that these compounds could intercalate into the cleaved DNA-binding site to form a TOP1-DNA-ligand ternary complex, and the ligand remained secure at the cleaved DNA-binding site to form a stable ternary complex. As the binding free energy of compound EVO-1 with TOP1 (-38.33 kcal·mol-1) was lower than that of compound EVO-6 (-33.25 kcal·mol-1), compound EVO-1 could be a more potent anti-gastric cancer agent than compound EVO-6. Discussion: Thus, compound EVO-1 could be a promising anti-gastric cancer drug candidate. This study may facilitate the design and development of novel TOP1 inhibitors.

Research Progress and Prospect of Nitrogen-containing Heterocycle in Anti-gastric Cancer Drugs: A Review.

Gastric cancer was the fifth most common cancer, and its drug treatment mainly included chemotherapy, targeted therapy, and immunotherapy. With the rise of immunotherapy in gastric cancer, small-molecule anti-gastric cancer drugs still have irreplaceable places because of many advantages, such as high stability and mass-productivity, high efficiency, and low cost. At present, the small-molecule anti-gastric cancer drugs in the clinic are constrained by their side effects. So, developing more novel anti-gastric cancer drugs with better efficacy and fewer side effects is urgently needed. Nitrogen-containing heterocycle molecules have attracted much attention from researchers due to their high biocompatibility, activity, and bioavailability, and they even could act with a unique mechanism. This review summarized various types of nitrogen-containing heterocycle antigastric cancer lead compounds from 2017 to 2022 in the last five years. Compared with monocyclic nitrogen-containing heterocycle and bicyclic nitrogen-containing heterocycle, the thick nitrogen-containing heterocycle applied as the skeleton not only showed high efficiency and low toxicity but also, interestingly, may have had some unique mechanism such as inhibition of aurora A and B kinases, etc. We propose two prospective and valuable strategies to develop more efficient candidates for anti-gastric cancer. One strategy was further optimized for some lead compounds mentioned in this review. The other strategy involved utilizing the "pseudo-natural products" concept proposed by Professor Wilhelm Waldmann, combining different nitrogen-containing heterocycle fragments in two and three-dimensional spaces to obtain new thick nitrogen-containing heterocycle skeletons. The strategy will contribute to the expansion of the thick nitrogenous heterocycle's framework, and it was expected that more novel mechanisms and more effective antigastric drugs could be found. These two strategies are expected to help researchers develop more anti-gastric cancer drugs with better potency and lower side effects.

Selenochemical modification of low molecular weight polysaccharides from Grifola frondosa and the mechanism of their inhibitory effects on gastric cancer cells.

An important micronutrient involved in immune response and antitumor is selenium. LMW-GFP, a polysaccharide extracted from Grifola frondosa seed bodies, has a relatively weak antitumor effect on BGC-823 and MFC cells in vitro, whereas selenium binding to LMW-GFP can significantly increase the in vitro antitumor activity of LMW-GFP. In this study, Se-LMW-GFP was prepared by the HNO3-Na2SeO3 method, and the structures of LMW-GFP and Se-LMW-GFP were characterized by UV-visible spectroscopy of absorption, FTIR spectroscopy, and electron scanning microscopy, and these structural analyses showed that selenium was successfully complexed to LMW-GFP. The selenium content of Se-LMW-GFP was measured to be 2.08 % ± 0.08 % by ICP-MS. The anti-tumor activity of LMW-GFP before and after selenium modification was compared by cellular experiments, and the findings indicated that the anti-tumor activity of Se-LMW-GFP was considerably improved over that of LMW-GFP, and inhibited the proliferation of BGC-823 cells and MFC cells through a combination of the Fas/FasL-mediated exogenous death receptor pathway as well as the endogenous mitochondrial pathway. Our results suggest that Se-LMW-GFP not only has great potential for natural health food and anti-gastric cancer drug development but is also a good selenium supplement.

Ligand-Based Design of Novel Quinoline Derivatives as Potential Anticancer Agents: An In-Silico Virtual Screening Approach.

In this study, using the Comparative Molecular Field Analysis (CoMFA) approach, the structure-activity relationship of 33 small quinoline-based compounds with biological anti-gastric cancer activity in vitro was analyzed in 3D space. Once the 3D geometric and energy structure of the target chemical library has been optimized and their steric and electrostatic molecular field descriptions computed, the ideal 3D-QSAR model is generated and matched using the Partial Least Squares regression (PLS) algorithm. The accuracy, statistical precision, and predictive power of the developed 3D-QSAR model were confirmed by a range of internal and external validations, which were interpreted by robust correlation coefficients (RTrain2=0.931; Qcv2=0.625; RTest2=0.875). After carefully analyzing the contour maps produced by the trained 3D-QSAR model, it was discovered that certain structural characteristics are beneficial for enhancing the anti-gastric cancer properties of Quinoline derivatives. Based on this information, a total of five new quinoline compounds were developed, with their biological activity improved and their drug-like bioavailability measured using POM calculations. To further explore the potential of these compounds, molecular docking and molecular dynamics simulations were performed in an aqueous environment for 100 nanoseconds, specifically targeting serine/threonine protein kinase. Overall, the new findings of this study can serve as a starting point for further experiments with a view to the identification and design of a potential next-generation drug for target therapy against cancer.

A robust and validated LC-MS/MS method for the quantification of ramucirumab in rat and human serum using direct enzymatic digestion without immunoassay.

A new liquid chromatography tandem mass spectrometry (LC-MS/MS) method was established to quantify the anti-gastric cancer fully human monoclonal antibody (ramucirumab) in rat and human serum. The surrogate peptide (GPSVLPLAPSSK) for ramucirumab was generated by trypsin hydrolysis and quantified using the isotopically labeled peptide GPSVLPLAPSSK[13C6, 15N2]ST containing two more amino acids at the carboxyl end as an internal standard to correct for variations introduced during the enzymatic hydrolysis process and any mass spectrometry changes. Additionally, the oxidation and deamidation of unstable peptides (VVSVLTVLHQDWLNGK and NSLYLQMNSLR) were detected. The quantitative range of the proposed method was 1-1000 µg/mL, and complete methodological validation was performed. The precision, accuracy, matrix effect, sensitivity, stability, selectivity, carryover, and interference of the measurements met the required standards. The validated LC-MS/MS method was applied to pharmacokinetic studies in rats administered ramucirumab at 15 mg/kg intravenously. Overall, a robust, efficient, and cost-effective LC-MS/MS method was successfully developed for quantifying ramucirumab in rat and human serum.

Identification of a novel heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) ligand that disrupts HnRNPA2B1/nucleic acid interactions to inhibit the MDMX-p53 axis in gastric cancer.

Gastric carcinoma is a highly malignant tumor that still lacks effective molecular targets. Heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) is an essential oncogenic driver overexpressed in various cancers. The potential role of hnRNPA2B1 in oncotherapy has not been revealed because of the absence of active chemical molecules. In this study, we identified the pseudourea derivative XI-011 as a novel hnRNPA2B1 ligand using chemical proteomics. An interaction study indicated that XI-011 could bind the nucleotide-binding domain to disrupt the recruitment of hnRNPA2B1 to the promoter and untranslated region of the murine double minute X (MDMX) gene, thereby inhibiting its transcription. In addition, chemical targeting of hnRNPA2B1 recovered inactivated p53 and enhanced the therapeutic efficacy of apatinib in vivo. This work presented a novel strategy to restore p53 activity for the treatment of gastric cancers via chemically targeting hnRNPA2B1.

Recent developments on natural polysaccharides as potential anti-gastric cancer substance: Structural feature and bioactivity.

Gastric cancer (GC) is being a serious threat to human health. Seeking safer and more effective ingredients for anti-GC is of significance. Increasing natural polysaccharides (NPs) have been demonstrated to possess anti-GC activity. However, the information on anti-GC NPs is scattered. For well-understanding the potential of NPs as anti-GC substances, the recent developments on structure, bioactivity and mechanism of anti-GC NPs were comprehensively reviewed in this article. Meanwhile, the structure-activity relationship was discussed. Recent studies indicated that anti-GC NPs could be mainly divided into glucan and heteropolysaccharide, whose structures affected by sources and protocols of extraction and purification. NPs exhibited anti-GC activities in cell and animal experiments as well as clinical trials, and the mechanisms might be anti-proliferation, inducing apoptosis, anti-metastasis and anti-invasion, inducing autophagy, boosting immunity, anti-angiogenesis, reducing drug resistance, anti-angiogenesis, improving antioxidant level and changing metabolites. Moreover, structural features included molecular weight, functional groups, uronic acid and monosaccharide composition, glycosidic linkage type, and degree of branching and conformation might influence the activities. Otherwise, modifications could enhance the anti-GC activity of NPs, and anti-GC NPs could be combinedly used with chemotherapeutic drugs. This review supports the applications of NPs in anti-GC and provides theoretical basis for future study.

Research Progress on the Mechanisms of Polysaccharides against Gastric Cancer.

Gastric cancer is a common type of cancer that poses a serious threat to human health. Polysaccharides are important functional phytochemicals, and research shows that polysaccharides have good anti-gastric cancer effects. We collated all relevant literature published from 2000 to 2020 and found that more than 60 natural polysaccharides demonstrate anti-gastric cancer activity. At the present, the sources of these polysaccharides include fungi, algae, tea, Astragalus membranaceus, Caulis Dendrobii, and other foods and Chinese herbal medicines. By regulating various signaling pathways, including the PI3K/AKT, MAPK, Fas/FasL, Wnt/ß-catenin, IGF-IR, and TGF-ß signaling pathways, polysaccharides induce gastric cancer cell apoptosis, cause cell cycle arrest, and inhibit migration and invasion. In addition, polysaccharides can enhance the immune system and killing activity of immune cells in gastric cancer patients and rats. This comprehensive review covers the extraction, purification, structural characterization, and mechanism of plant and fungal polysaccharides against gastric cancer. We hope this review is helpful for researchers to design, research, and develop plant and fungal polysaccharides.

S3I-201 derivative incorporating naphthoquinone unit as effective STAT3 inhibitors: Design, synthesis and anti-gastric cancer evaluation.

Signal transducer and activator of transcription 3 (STAT3) is a key regulator of many human cancers and has been widely recognized as a promising target for cancer therapy. A variety of small-molecule inhibitors have been developed for targeting STAT3, and some of them are now undergoing clinical trials. S3I-201, a known STAT3 inhibitor, may block STAT3 function in cancer cells by binding to the STAT3 SH2 domain to disrupt STAT3 protein complex formation. Using S3I-201 as a starting point for drug development, we synthesized a series of new STAT3 inhibitors 9a-x in this study by introducing naphthoquinone unit, a privileged fragment in STAT3 inhibitors. Most of the compounds exhibited strong anti-proliferation activity of gastric cancer cells (MGC803, MKN28, MNK1, and AGS). The representative compound 9n (SIL-14) could effectively inhibit the colony formation and migration of gastric cancer cells MGC803, arrest the cell cycle and induce MGC803 cell apoptosis at low micromolar concentrations in vitro. In addition, SIL-14 can also inhibit the phosphorylation of STAT3 protein and significantly decrease the expression of total STAT3, suggesting that it may exert anticancer effects by blocking the STAT3 signaling pathway. These results support that SIL-14 may be a promising STAT3 inhibitor for the further development of potential anti-gastric cancer candidates.

Poria Acid, Triterpenoids Extracted from Poria cocos, Inhibits the Invasion and Metastasis of Gastric Cancer Cells.

BACKGROUND: Poria cocos (P. cocos) is an important medicinal fungus in traditional Chinese medicine. Poria acid (PA), a triterpenoid compound, is an effective component of traditional Chinese medicine P. cocos. This experiment investigated the anti-gastric cancer biological activity of PA in vitro. METHODS: The effect of PA on the viability of gastric cancer cells was detected by the thiazolyl blue (MTT) assay. Cell adhesion assays were used to detect changes in the adhesion of cells treated after PA (0, 20, 40, and 80 µmol/L). The ability of cell invasion and migration were detected by Transwell assays and wound healing assays. A high-content imaging system was used to dynamically record the motility of the gastric cancer cells after PA (0, 20, 40, and 80 µmol/L) treatment. Western blotting was used to detect the expression of epithelial-mesenchymal transformation (EMT), invasion and migration related proteins. RESULTS: The MTT assay showed that the proliferation of gastric cancer cells was significantly inhibited after PA treatment. Cell adhesion experiments showed that the adhesion of gastric cancer cells was significantly decreased after PA treatment. Compared with the control group, the wound healing area of the gastric cancer cells treated with different concentrations of PA decreased. The Transwell assay showed that the number of gastric cancer cells passing through the cell membrane were significantly reduced after PA treatment. In addition, after PA treatment, the cells' movement distance and average movement speed were significantly lower than those of the control group. Finally, PA can significantly alter the expression of EMT-related proteins E-cadherin, N-cadherin, and Vimentin and decreased the expressions of metastasis-related proteins matrix metalloproteinase (MMP) 2, MMP-9 and tissue inhibition of matrix metalloproteinase (TIMP)1 in the gastric cancer cells. CONCLUSIONS: Triterpenoids from P. cocos have significant biological activity against gastric cancer, and the mechanism may be involved in the process of epithelial-mesenchymal transformation.

Design, synthesis and biological evaluation of novel 2-(4-(1H-indazol-6-yl)-1H-pyrazol-1-yl)acetamide derivatives as potent VEGFR-2 inhibitors.

Vascular endothelial growth factor-2 (VEGFR-2) plays a pivotal role in tumor angiogenesis. Herein, a library of novel 2-(4-(1H-indazol-6-yl)-1H-pyrazol -1-yl)acetamide derivatives were designed and synthesized as VEGFR-2 inhibitors based on scaffold hopping strategy. These compounds exhibited the excellent inhibitory in both VEGFR-2 and tumor cells proliferation. Especially, compound W13 possessed potent VEGFR-2 inhibition with IC50 = 1.6 nM and anti-proliferation against HGC-27 tumor cells with IC50 = 0.36 ± 0.11 µM, as well as less toxicity against normal GES-1 cells with IC50 = 187.46 ± 10.13 µM. Moreover, W13 obviously inhibited colony formation, migration and invasion of HGC-27 cells by adjusting the expression of MMP-9 and E-cadherin, and induced HGC-27 cells apoptosis by increasing ROS production and regulating the expression of apoptotic proteins. Furthermore, W13 blocked the PI3K-Akt-mTOR signaling pathway in HGC-27 cells. In addition, anti-angiogenesis of W13 was proved by inhibiting tube formation and the expression of p-VEGFR-2 in HUVEC cells. All the results demonstrated that W13 could be developing as a promising anticancer agent for gastric cancer therapy.

Anticancer Applications and Pharmacological Properties of Piperidine and Piperine: A Comprehensive Review on Molecular Mechanisms and Therapeutic Perspectives.

Piperine and piperidine are the two major alkaloids extracted from black pepper (Piper nigrum); piperidine is a heterocyclic moiety that has the molecular formula (CH2)5NH. Over the years, many therapeutic properties including anticancer potential of these two compounds have been observed. Piperine has therapeutic potential against cancers such as breast cancer, ovarian cancer, gastric cancer, gliomal cancer, lung cancer, oral squamous, chronic pancreatitis, prostate cancer, rectal cancer, cervical cancer, and leukemia. Whereas, piperidine acts as a potential clinical agent against cancers, such as breast cancer, prostate cancer, colon cancer, lung cancer, and ovarian cancer, when treated alone or in combination with some novel drugs. Several crucial signalling pathways essential for the establishment of cancers such as STAT-3, NF-κB, PI3k/Aκt, JNK/p38-MAPK, TGF-ß/SMAD, Smac/DIABLO, p-IκB etc., are regulated by these two phytochemicals. Both of these phytochemicals lead to inhibition of cell migration and help in cell cycle arrest to inhibit survivability of cancer cells. The current review highlights the pharmaceutical relevance of both piperine and piperidine against different types of cancers.

Structural features and anti-gastric cancer activity of polysaccharides from stem, root, leaf and flower of cultivated Dendrobium huoshanense.

The structure features and anti-gastric cancer activities in vitro of stem, root, leaf and flower polysaccharides from cultivated Dendrobium huoshanense were investigated systematically. Stem polysaccharide (cDHPS) was composed of →4)-ß-D-Glcp-(1→, →4)-ß-D-Manp-(1→, →4)-3-O-acetyl-ß-D-Manp-(1→ with the molecular weight of 2.59 × 105 Da; root polysaccharide (cDHPR) was composed of →3,5)-α-L-Araf-(1→, →4)-ß-D-Glcp-(1→, →4)-ß-D-Manp-(1→, →4,6)-ß-D-Manp-(1→, →6)-α-D-Galp-(1→ and terminal ß-L-Araf with the molecular weight of 1.41 × 104 Da; leaf polysaccharide (cDHPL) was composed of →4)-ß-D-Glcp-(1→, →4)-ß-D-Manp-(1→, →4)-3-O-acetyl-ß-D-Manp-(1→, →3,6)-ß-D-Manp-(1→ and terminal α-D-Galp with the molecular weight of 2.09 × 105 Da; and flower polysaccharide (cDHPF) was composed of →4)-ß-D-Glcp-(1→, →4)-ß-D-Manp-(1→, →3,6)-ß-D-Manp-(1→ and terminal α-D-Galp with the molecular weight of 4.78 × 105 Da. Among these four polysaccharides, cDHPS showed the best anti-gastric cancer activity evidenced by the inhibited growth and c-myc expression as well as the enhanced apoptosis and p53 expression of murine forestomach carcinoma (MFC) cells, suggesting their difference in anti-gastric cancer activity should be contributed to their difference in structure features.

Novel tertiary sulfonamide derivatives containing benzimidazole moiety as potent anti-gastric cancer agents: Design, synthesis and SAR studies.

With the expectation to find out new anti-gastric cancer agents with high efficacy and selectivity, a series of novel tertiary sulfonamide derivatives were synthesized and the anti-cancer activity was studied in three selected cancer cell lines (MGC-803, PC-3, MCF-7) in vitro. Some of the synthesized compounds could significantly inhibit the proliferation of these tested cancer cells and were more potent than the positive control (5-Fu). The structure-activity relationship of tertiary sulfonamide derivatives was explored in this report. Among the tested compounds, compound 13g containing benzimidazole moiety showed the best anti-proliferation activities against MGC-803 cells (IC50 = 1.02 µM), HGC-27 cells (IC50 = 1.61 µM), SGC-7901 (IC50 = 2.30 µM) cells as well as the good selectivity between the cancer and normal cells. Cellular mechanism studies elucidated compound 13g inhibited the colony formation of gastric cancer cell lines. Meanwhile, compound 13g arrested cell cycle at G2/M phase and induced cell apoptosis. Mechanistically, compound 13g markedly decreased p-Akt and p-c-Raf expression, which revealed that compound 13g targeted gastric cancer cell lines via interfering with AKT/mTOR and RAS/Raf/MEK/ERK pathways. All the findings suggest that compound 13g might be a valuable lead compound for the anti-gastric cancer agents.

Novel 3-(2,6,9-trisubstituted-9H-purine)-8-chalcone derivatives as potent anti-gastric cancer agents: Design, synthesis and structural optimization.

To explore anti-gastric cancer agents with high efficacy and selectivity, we report the design, synthesis and optimization of a novel series of 3-(2,6,9-trisubstituted-9H-purine)-8-chalcone derivatives starting from the compound PCA-15 reported by us previously. Most of the target compounds demonstrated significant antiproliferative effects on MGC803 cancer cell line, and more potent than the positive control (PCA-15 and 5-Fu). Among them, compound 6o was identified to be the most active compound against MGC803 cell line with an IC50 value of 0.84 µM. Additionally, high selectivity was also observed between cancer and normal cells (23.35 µM against GES-1). Further mechanism studies confirmed that compound 6o could inhibit colony formation and migration, induce the apoptosis of MGC803 cells through both the mitochondrial-mediated intrinsic pathway and death receptor-mediated extrinsic pathway, which were evidenced by the up-regulation of Bax, cleaved-caspase 9/3/8, cleaved PARP and down-regulation of Bcl-2. Our systematic studies implied a new scaffold targeting gastric cancer cells for further development of small-molecule compounds with improved potency and selectivity.

Synthesis of (1E,4E)-1,5-bis(2,3-dimethoxyphenyl)penta-1,4-dien-3-one Analogs and Its Anti-gastric Cancer Activity In Vitro / 中国药学杂志

OBJECTIVE: To explore the efficient and economical synthesis method of asymmetric monocarbonyl curcumin ana-logues(AMCACs), design and sgnthesize a series of B19(1E, 4E)-1, 5-bis(2,3-dimethoxyphenyl) penta-1, 4-dien-3-one analogs to in- vestigate their anti-gastric cancer activities in vitro. METHODS: A series of asymmetric B19 analogues containing 2, 3-dimethoxyphenyl were designed via the combination principle of medicinal chemistry, and obtained a method for synthesizing intermediate (E)-2-(2, 3- dimethoxybenzylidene) cyclopentanone by one step catalyzed by L-proline. The targeted compounds were screened by MTT as-say, and colony cloning experiments were used to further verify its anti-gastric cancer activity in vitro. RESULTS: Ten novel target compounds were synthesized, and the structures were confirmed by LC-MS and 1H-NMR spectral analysis Among them, compound 6e had the highest inhibitory activity on the growth of gastric cancer cells SGC-7901 and BGC-823, whose IC50 were 9.80 and 13.50 μmol• L 1, respectively. CONCLUSION: L-proline could be used as a catalyst to synthesize asymmetric monocarbonyl curcumin analogues efficiently and economically Compound 6e could effectively inhibit the growth of gastric cancer cells in vitro, and its toxicity and inhibition mechanism of tumor cell growth need to be further studied.

In vitro and in vivo anti-tumor effects of a combination therapy of curcumin and celastrol to gastric cancer / 中成药

AIM To evaluate anti-gastric cancer effects and benefits of the combination therapy of celastrol and curcumin in vitro and in vivo.METHODS Curcumin,celastrol and curcumin + celastrol applied to BGC823 gastric cancer cells had their impact on the cells growth and apoptosis in vitro checked by CCK-8 assay and flow cytometry of AnnexinV-FITC/PI;and their in vivo anti-tumor effect,systemic toxicity,and influence to the survival time evaluated by using BGC823-bearing gastric tumor mouse models induced by subcutaneous implantation.RESULTS IC50 of curcumin,celastrol and curcumin + celastrol on BGC823 cell were found to be at (57.47 ± 5.22),(2.11 ±0.07) and (0.22 ±0.01) μmol/L,respectively.Curcumin + celastrol achieved a most optimal BGC823 cell apoptosis rate of (73.07 ±3.82)％ at concentrations of (10 mol/L +2 mol/L);and they left a positive impact on the BGC823 gastric tumor-bearing mice,given a (64.87 ±4.16)％ inhibitory rate,and a 50.5-day median survival time.Additionally,the combination therapy demonstrated its less side effects in terms of the body weight,spleen and liver of the nude mice,and significantly improved serum concentrations of TNF-α and IL-6.CONCLUSION Combination of curcumin and celastrol shows significantly synergistic anti-gastric cancer effects in vitro and in vivo.

GC-MS fingerprint of in vitro anti-gastric cancer active parts from roots of Uygur medicine Ferula ferulaeoides / 中草药

Objective: To preliminarily ascertain the anti-gastric cancer active parts from the roots of Ferula ferulaeoide and to study its GC-MS fingerprint Methods: The inhibitory effects of different extraction from the roots of F. ferulaeoide on the cell proliferation of SGC-7901 cells were determined with MTT colorimetric method. GC-MS fingerprint of in vitro anti-gastric cancer active parts from F. ferulaeoide was investigated and analyzed by GC-MS and principal component analysis (PCA). Results: The chloroform extract showed the best inhibition on the growth of SGC-7901 cells. The method on GC-MS fingerprint of in vitro anti-gastric cancer active parts from F. ferulaeoide was established, showing 28 common characteristic peaks. The PCA demonstrated that the common peaks 1, 2, 4, 6, 7, 8, 9, 12, 21, 22, and 23 were connected closely with the in vitro anti-gastric cancer activity, and the seven compounds were 3-methoxy-1,2-propanediol, D-limonene, L-borneol acetate, terpinyl acetate, 1,5,9-undecatriene, 2,6,10-trimethyl, α-cedrene, and a-bergsmotene, β-cedrene, 8-epi-γ-eudesmol, γ-eudesmol, hinesol. Totally 28 common compounds of 10 batches of samples accounted for over 92% of the volatile contents, and the similarity of the GC-MS fingerprints from the 10 batches of samples was over 0.90. Conclusion: The chloroform extract from the roots of F. ferulaeoides with potential inhibitory effect on gastric cancer SGC-7901 cells is tentatively confirmed, and needs further to verify by animal cells in vivo. The method of GC-MS fingerprinting is rapid, simple, and accurate with good reproducibility and stability, and can be used to control the quality of active parts of F. ferulaeoides.