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1.
J Ethnopharmacol ; : 118516, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38971341

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Calotropis gigantea (L.) Dryand. (C. gigantea) is a traditional medicinal plant, recognized for its effectiveness in managing diabetes, along with its notable antioxidant, anti-inflammatory, and anticancer properties. Type II diabetes mellitus (T2DM) is characterized by chronic metabolic disorders associated with an elevated risk of hepatocellular carcinoma (HCC) due to hyperglycemia and impaired insulin response. The scientific validation of C. gigantea's ethnopharmacological efficacy offers advantages in alleviating cancer progression in T2DM complications, enriching existing knowledge and potentially aiding future clinical cancer treatments. AIM: This study aimed to investigate the preventive potential of the dichloromethane fraction of C. gigantea stem bark extract (CGDCM) against diethylnitrosamine (DEN)-induced HCC in T2DM rats, aiming to reduce cancer incidence associated with diabetes while validating C. gigantea's ethnopharmacological efficacy. MATERIALS AND METHODS: Spontaneously Diabetic Torii (SDT) rats were administered DEN to induce HCC (SDT-DEN-VEH), followed by treatment with CGDCM. Metformin was used as a positive control (SDT-DEN-MET). All the treatments were administered for 10 weeks after the initial DEN injection. Diabetes-related parameters, including serum levels of glucose, insulin, and glycosylated hemoglobin (HbA1c), as well as liver function enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase), were quantified. Serum inflammation biomarkers interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were evaluated. Liver tissue samples were analyzed for inflammation protein expression (IL-6, TNF-α, transforming growth factor-ß1 (TGF-ß1), and α-smooth muscle actin (α-SMA)). Histopathological evaluation was performed to assess hepatic necrosis, inflammation, and fibrosis. Liver cell proliferation was determined using immunohistochemistry for Ki-67 expression. RESULTS: Rats with SDT-DEN-induced HCC treated with CGDCM exhibited reduced serum glucose levels, elevated insulin levels, and decreased HbA1c levels. CGDCM treatment also reduced elevated hepatic IL-6, TNF-α, TGF-ß1, and α-SMA levels in SDT-DEN-VEH rats. Additionally, CGDCM treatment prevented hepatocyte damage, fibrosis, and cell proliferation. No adverse effects on normal organs were observed with CGDCM treatment, suggesting its safety for the treatment of HCC complications associated with diabetes. Additionally, the absence of adverse effects in SD rats treated with CGDCM at 2.5 mg/kg further supports the notion of its safe usage. CONCLUSIONS: These findings suggest that C. gigantea stem bark extract exerts preventive effects against the development of HCC complications in patients with T2DM, expanding the potential benefits of its ethnopharmacological advantages.

2.
PLoS One ; 19(3): e0300051, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38527038

RESUMO

The cytotoxicity of the ethyl acetate fraction of the Calotropis gigantea (L.) Dryand. (C. gigantea) stem bark extract (CGEtOAc) has been demonstrated in many types of cancers. This study examined the improved cancer therapeutic activity of sorafenib when combined with CGEtOAc in HepG2 cells. The cell viability and cell migration assays were applied in HepG2 cells treated with varying concentrations of CGEtOAc, sorafenib, and their combination. Flow cytometry was used to determine apoptosis, which corresponded with a decline in mitochondrial membrane potential and activation of DNA fragmentation. Reactive oxygen species (ROS) levels were assessed in combination with the expression of the phosphatidylinositol-3-kinase (PI3K)/ protein kinase B (Akt)/ mammalian target of rapamycin (mTOR) pathway, which was suggested for association with ROS-induced apoptosis. Combining CGEtOAc at 400 µg/mL with sorafenib at 4 µM, which were their respective half-IC50 concentrations, significantly inhibited HepG2 viability upon 24 h of exposure in comparison with the vehicle and each single treatment. Consequently, CGEtOAc when combined with sorafenib significantly diminished HepG2 migration and induced apoptosis through a mitochondrial-correlation mechanism. ROS production was speculated to be the primary mechanism of stimulating apoptosis in HepG2 cells after exposure to a combination of CGEtOAc and sorafenib, in association with PI3K/Akt/mTOR pathway suppression. Our results present valuable knowledge to support the development of anticancer regimens derived from the CGEtOAc with the chemotherapeutic agent sorafenib, both of which were administered at half-IC50, which may minimize the toxic implications of cancer treatments while improving the therapeutic effectiveness toward future medical applications.


Assuntos
Acetatos , Calotropis , Neoplasias Hepáticas , Humanos , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células Hep G2 , Calotropis/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Casca de Planta/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Apoptose , Linhagem Celular Tumoral , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo
3.
Heliyon ; 9(7): e18013, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37483695

RESUMO

Calotropis gigantea stem bark extract, particularly the dichloromethane fraction (CGDCM), demonstrated the most potent antiproliferative effects on hepatocellular carcinoma HepG2 and colorectal HCT116 cells. The current study focused on enhancing the effectiveness of cancer treatment with CGDCM at concentrations close to the IC50 in HCT116 cells by reducing their nutrient supply. CGDCM (2, 4, and 8 µg/mL) treatment for 24 h under glucose conditions of 4.5 g/L without fetal bovine serum (FBS) supplementation or serum starvation (G+/F-), glucose 0 g/L with 10% FBS or glucose starvation (G-/F+), and glucose 0 g/L with 0% FBS or complete starvation (G-/F-) induced a greater antiproliferative effect in HCT116 cells than therapy in complete medium with glucose 4.5 g/L and 10% FBS (G+/F+). Nonetheless, the anticancer effect of CGDCM at 4 µg/mL under (G-/F-) showed the highest activity compared to other starvation conditions. The three starvation conditions showed a significant reduction in cell viability compared to the control (G+/F+) medium group, while the inhibitory effect on cell viability did not differ significantly among the three starvation conditions. CGDCM at 4 µg/mL in (G-/F-) medium triggered apoptosis by dissipating the mitochondrial membrane potential and arresting cells in the G2/M phase. This investigation demonstrated that a decrease in intracellular ATP and fatty acid levels was associated with enhanced apoptosis by treatment with CGDCM at 4 µg/mL under (G-/F-) conditions. In addition, under (G-/F-), CGDCM at 4 µg/mL increased levels of reactive oxygen species (ROS) and was suggested to primarily trigger apoptosis in HCT116 cells. Thus, C. gigantea extracts may be useful for the future development of alternative, effective cancer treatment regimens.

4.
Heliyon ; 9(5): e16375, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37251821

RESUMO

The 95% ethanolic extract of the dry powder of Calotropis gigantea (C. gigantea) stem bark was separated by fractionation with different solutions to yield 4 fractions: dichloromethane (CGDCM), ethyl acetate (CGEtOAc), and water (CGW). This research focused on CGDCM-induced apoptosis in HepG2 cells with IC50 and above-IC50 values, which provide useful information for future anticancer applications. CGDCM had lower cytotoxicity on normal lung fibroblast IMR-90 cells than on HepG2 cells. Apoptotic induction of CGDCM was mediated by decreased fatty acid and ATP synthesis while increasing reactive oxygen species production. The effects of the four extracts on the activity of the four major CYP450 isoforms (CYP1A2, CYP2C9, CYP2E1 and CYP3A4) were determined using the CYP-specific model activity of each isoform. All four fractions of the extract were shown to be poor inhibitors of CYP1A2 and CYP2E1 (IC50 > 1000 µg/mL) and moderate inhibitors of CYP3A4 (IC50 = 56.54-296.9 µg/mL). CGDCM and CGW exerted moderate inhibition activities on CYP2C9 (IC50 = 59.56 and 46.38 µg/mL, respectively), but CGEtOH and CGEtOAc exhibited strong inhibition activities (IC50 = 12.11 and 20.43 µg/mL, respectively). It is proposed that C. gigantea extracts at high doses have potential for further studies to develop alternative anticancer applications. Inhibiting CYP2C9 activity may also lead to drug-herb interactions.

5.
Sci Rep ; 12(1): 12151, 2022 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-35840761

RESUMO

Several fractions of Calotropis gigantea extracts have been proposed to have potential anticancer activity in many cancer models. The present study evaluated the anticancer activity of C. gigantea stem bark extracts in liver cancer HepG2 cells and diethylnitrosamine (DEN)-induced primary liver cancer in rats. The carcinogenesis model induced by DEN administration has been widely used to study pathophysiological features and responses in rats that are comparable to those seen in cancer patients. The dichloromethane (CGDCM), ethyl acetate, and water fractions obtained from partitioning crude ethanolic extract were quantitatively analyzed for several groups of secondary metabolites and calactin contents. A combination of C. gigantea stem bark extracts with doxorubicin (DOX) was assessed in this study to demonstrate the enhanced cytotoxic effect to cancer compared to the single administration. The combination of DOX and CGDCM, which had the most potential cytotoxic effect in HepG2 cells when compared to the other three fractions, significantly increased cytotoxicity through the apoptotic effect with increased caspase-3 expression. This combination treatment also reduced ATP levels, implying a correlation between ATP and apoptosis induction. In a rat model of DEN-induced liver cancer, treatment with DOX, C. gigantea at low (CGDCM-L) and high (CGDCM-H) doses, and DOX + CGDCM-H for 4 weeks decreased the progression of liver cancer by lowering the liver weight/body weight ratio and the occurrence of liver hyperplastic nodules, fibrosis, and proliferative cells. The therapeutic applications lowered TNF-α, IL-6, TGF-ß, and α-SMA inflammatory cytokines in a similar way, implying that CGDCM had a curative effect against the inflammation-induced liver carcinogenesis produced by DEN exposure. Furthermore, CGDCM and DOX therapy decreased ATP and fatty acid synthesis in rat liver cancer, which was correlated with apoptosis inhibition. CGDCM reduced cleaved caspase-3 expression in liver cancer rats when used alone or in combination with DOX, implying that apoptosis-inducing hepatic carcinogenesis was suppressed. Our results also verified the low toxicity of CGDCM injection on the internal organs of rats. Thus, this research clearly demonstrated a promising, novel anticancer approach that could be applied in future clinical studies of CGDCM and combination therapy.


Assuntos
Calotropis , Neoplasias Hepáticas , Trifosfato de Adenosina/metabolismo , Animais , Carcinogênese/metabolismo , Caspase 3/metabolismo , Dietilnitrosamina/toxicidade , Doxorrubicina/uso terapêutico , Fígado/metabolismo , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Casca de Planta/metabolismo , Extratos Vegetais/uso terapêutico , Ratos
6.
FEBS Open Bio ; 12(5): 937-958, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35243817

RESUMO

The de novo lipogenesis (DNL) pathway has been identified as a regulator of cancer progression and aggressiveness. Downregulation of key lipogenesis enzymes has been shown to activate apoptosis in cancerous cells. Epigallocatechin gallate (EGCG) inhibits cancer cell proliferation without causing cytotoxicity in healthy cells. The present study aimed to investigate the effects of EGCG on the promotion of apoptosis associated with the DNL pathway inhibition in cancer cells, both in vitro and in vivo. We observed that two colorectal cancer cell lines (HCT116 and HT-29) had a higher cytotoxic response to EGCG treatment than hepatocellular carcinoma cells, including HepG2 and HuH-7. EGCG treatment decreased cell viability and increased mitochondrial damage-triggered apoptosis in both HCT116 and HT-29 cancer cells. Additionally, we treated mice transplanted with HCT116 cells with 30 or 50 mg·kg-1 EGCG for 7 days to evaluate the apoptotic effects of EGCG treatment in a xenograft mouse model of cancer. We observed a decrease in intracellular fatty acid levels, which suggested that EGCG-induced apoptosis was associated with a decrease in fatty acid levels in cancer. Suppression of ATP synthesis by EGCG indicated that cell death induction in cancer cells could be mediated by shared components of the DNL and energy metabolism pathways. In addition, EGCG-induced apoptosis suppressed the expression of the phosphorylation protein kinase B and extracellular signal-regulated kinase 1/2 signaling proteins in tumors from xenografted mice. Cytotoxic effects in unaffected organs and tissues of the mouse xenograft model were absent upon EGCG treatment.


Assuntos
Catequina , Neoplasias Colorretais , Animais , Apoptose , Catequina/análogos & derivados , Catequina/farmacologia , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Ácidos Graxos , Humanos , Lipogênese , Camundongos
7.
PLoS One ; 16(8): e0254392, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34343190

RESUMO

Conventional chemotherapeutic agents for colorectal cancer (CRC) cause systemic side effects and eventually become less efficacious owing to the development of drug resistance in cancer cells. Therefore, new therapeutic regimens have focused on the use of natural products. The anticancer activity of several parts of Calotropis gigantea has been reported; however, the effects of its stem bark extract on inhibition of cancer cell proliferation have not yet been examined. In this study, the anticancer activity of C. gigantea stem bark extract, both alone and in combination with 5-fluorouracil (5-FU), was evaluated. A crude ethanolic extract was prepared from dry, powdered C. gigantea barks using 95% ethanol. This was then partitioned to obtain dichloromethane (CGDCM), ethyl acetate, and water fractions. Quantitative analysis of the constituent secondary metabolites and calotropin was performed. These fractions exhibited cytotoxicity in HCT116 and HT-29 cells, with CGDCM showing the highest potency in both the cell lines. A combination of CGDCM and 5-FU significantly enhanced the cytotoxic effect. Moreover, the resistance of normal fibroblast, HFF-1, cells to this combination demonstrated its safety in normal cells. The combination significantly enhanced apoptosis through the mitochondria-dependent pathway. Additionally, the combination reduced adenosine triphosphate production and increased the production of reactive oxygen species, demonstrating the mechanisms involved in the induction of apoptosis. Our results suggest that CGDCM is a promising anti-cancer agent and may enhance apoptosis induction by 5-FU in the treatment of CRC, while minimizing toxicity toward healthy cells.


Assuntos
Trifosfato de Adenosina/metabolismo , Apoptose/efeitos dos fármacos , Calotropis/química , Neoplasias do Colo/metabolismo , Casca de Planta/química , Extratos Vegetais/farmacologia , Caules de Planta/química , Espécies Reativas de Oxigênio/metabolismo , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Células HCT116 , Células HT29 , Humanos , Extratos Vegetais/química
8.
J Tradit Complement Med ; 11(4): 356-368, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34195030

RESUMO

BACKGROUND AND AIM: Metabolic disease encompasses most contemporary non-communicable diseases, especially cardiovascular and fatty liver disease. Mulberry fruits of Morus alba L. are a favoured food and a traditional medicine. While they are anti-atherosclerotic and reduce hyperlipidemic risk factors, studies need wider scope that include ameliorating cardiovascular and liver pathologies if they are to become clinically effective treatments. Therefore, the present study sought to show that freshly dried mulberry fruits (dMF) might counteract the metabolic/cardiovascular pathologies in mice made hyperlipidemic by high-fat diet (HF). EXPERIMENTAL PROCEDURE: C57BL/6J mice were fed for 3 months with either: i) control diet, ii) HF, iii) HF+100 mg/kg dMF, or iv) HF+300 mg/kg dMF. Body weight gain, food intake, visceral fat accumulation, fasting blood glucose, plasma lipids, and aortic, heart, and liver histopathologies were evaluated. Adipocyte lipid accumulation, autophagy, and bile acid binding were also investigated. RESULTS AND CONCLUSION: HF increased food intake, body weight, visceral fat, plasma total cholesterol (TC) and low-density lipoprotein (LDL), TC/HDL ratio, blood glucose, aortic collagen, arterial and cardiac wall thickness, and liver lipid. Both dMF doses prevented hyperphagia, body weight gain, and visceral fat accumulation, lowered blood glucose, plasma TG and unfavourable TC/HDL and elevated plasma HDL beyond baseline. Arterial and cardiac wall hypertrophy, aortic collagen fibre accumulation and liver lipid deposition ameliorated in dMF-fed mice. Clinical trials on dMF are worthwhile but outcomes should be holistic commensurate with the constellation of disease risks. Here, dMF should supplement the switch to nutrient-rich from current energy-dense diets that are progressively crippling national health systems.

9.
Mol Clin Oncol ; 4(6): 925-928, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27284424

RESUMO

Sialoblastoma is a rare salivary gland tumor that recapitulates the primitive salivary gland anlage. The authors herein report a case of sialoblastoma of a minor salivary gland, clinically presenting with progressive enlargement of a mass in the cheek of a 1-year-old female infant. Histopathologically, the mass consisted of tight clusters of basaloid cells and partially formed ductal and pseudo-ductal spaces separated by thin fibrous bands. Immunohistchemical studies demonstrated the presence of cytokeratin AE1/AE3, p63, CD99, α-fetoprotein (AFP) and Hep Par-1 expression in a considerable number of tumor cells. The clinical and pathological characteristics are presented and relevant literature is reviewed. Early complete surgical excision is recommended for the treatment of sialoblastoma. Radiation may be considered in cases with incomplete resection of the tumor. Chemotherapy may play a vital role in extensive, metastatic, or relapsed cases, or in cases with inadequate excision. The follow-up treatment should be frequent and prolonged. To the best of our knowledge, this is the first reported case of sialoblastoma of the cheek with immunoreactivity for AFP and Hep Par-1, which may be associated with the embryonic origin of the tumor. AFP may be a useful marker of tumor response in patient with sialoblastoma.

10.
Mol Clin Oncol ; 5(6): 853, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28101362

RESUMO

[This corrects the article DOI: 10.3892/mco.2016.840.].

11.
J Med Assoc Thai ; 95 Suppl 10: S226-9, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23451467

RESUMO

Enchondroma is a benign tumor that is generally asymptomatic and rarely found in the talus. A forty-nine-year-old man, had a chronic left ankle pain which related to moderate to heavy activity. A plain radiograph and magnetic resonance imaging (MRI) revealed a 1.3 cm benign lobulated intramedullary lesion at the middle 1/3 of medial part of talar dome with sclerotic rim. An arthroscopic intralesional curettage of the ankle joint was performed without bone grafting. Histologic examination was consistent with the diagnosis of an enchondroma. The patient was asymptomatic and without restriction on his job at 6 months. At 1 year of follow-up, the CT scan and MRI demonstrated no recurrence of the tumor but the defect was not filled up.


Assuntos
Artroscopia/métodos , Neoplasias Ósseas/cirurgia , Condroma/cirurgia , Doenças do Pé/cirurgia , Tálus , Neoplasias Ósseas/diagnóstico , Condroma/diagnóstico , Doenças do Pé/diagnóstico , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
12.
J Med Assoc Thai ; 88(6): 849-54, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16083229

RESUMO

Primary peritoneal adenosarcoma with sarcomatous overgrowth and fetal-type cartilage presented in a 48-year-old female patient is described. The tumor seems likely to have derived from the pelvic peritoneum, wheareas the uterus, ovaries and tubes were uninvolved. It was composed of benign-appearing glands and a sarcomatous component showing cartilaginous differentiation. The extrauterine adenosarcomas were reported in other sites, e.g. cervix, ovary, fallopian tube, bladder, and peritoneum. This case was the ninth case of the primary peritoneal adenosarcoma in the English literature and the first report in Thailand.


Assuntos
Adenossarcoma/patologia , Cartilagem/patologia , Neoplasias Peritoneais/patologia , Adenossarcoma/diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Peritoneais/diagnóstico
13.
J Med Assoc Thai ; 88(8): 1128-33, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16404844

RESUMO

Anorectal malignant melanoma is a rare disease and has a uniformly poor prognosis. The following are two reported cases from Buddhachinaraj Hospital. A 55-year-old and a 65-year-old female patients presented with rectal bleeding. Large anorectal masses with regional lymph node involvement were detected initially. They exhibited different histological features which were atypical round cell resembling lymphocytes or were small cell appearance and spindle cell appearance similar to sarcoma. The diagnosis was confirmed by expression of S100 protein and HMB45. Abdominoperineal resection (APR) was the treatment of choice in both patients. The former case died in the fourth month after diagnosis because of distance metastasis and congestive heart failure. The latter case is receiving postoperative adjuvant therapy.


Assuntos
Neoplasias do Ânus/patologia , Melanoma/patologia , Neoplasias Retais/patologia , Idoso , Neoplasias do Ânus/cirurgia , Evolução Fatal , Feminino , Humanos , Melanoma/cirurgia , Pessoa de Meia-Idade , Prognóstico , Neoplasias Retais/cirurgia , Tailândia
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