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Solanum incanum extract (SR-T100) induces melanoma cell apoptosis and inhibits established lung metastasis.

ABSTRACT: Melanoma, a cancer derived from melanocytes, is one of the most chemoresistant cancers and tends to metastasize. Once it metastasizes, the prognosis is poor. Even with the recent advancement of targeted therapy and immunotherapy, the prognosis remains discouraging. SR-T100, a Solanum incanum extract, shows anticancer effects against several cancers; however, its therapeutic efficacy against melanoma and established metastasis remains unknown. In this study, we showed that SR-T100 induces apoptosis, DNA damage, and G0/G1 cell cycle arrest in murine B16 melanoma cells in vitro. In vivo, intralesional injection of SR-T100 decreased the tumor size of the regional melanoma in the foot pad. Moreover, intraperitoneal injection of SR-T100 inhibited the growth and the number of established melanoma metastases in the lungs. Our study highlights SR-T100 as a potential novel treatment for established tumors from regional and metastatic melanoma.

SUBMITTER: Yu S

PROVIDER: S-EPMC5732746 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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<i>Solanum incanum</i> extract (SR-T100) induces melanoma cell apoptosis and inhibits established lung metastasis.

Yu Sebastian S Sheu Hamm-Ming HM Lee Chih-Hung CH

Oncotarget 20171004 61

Melanoma, a cancer derived from melanocytes, is one of the most chemoresistant cancers and tends to metastasize. Once it metastasizes, the prognosis is poor. Even with the recent advancement of targeted therapy and immunotherapy, the prognosis remains discouraging. SR-T100, a <i>Solanum incanum</i> extract, shows anticancer effects against several cancers; however, its therapeutic efficacy against melanoma and established metastasis remains unknown. In this study, we showed that SR-T100 induces ...[more]

PMID: 29262580

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Project description:BackgroundWithania somnifera is an Indian medicinal herb known for the multipotential ability to cure various therapeutic ailments as described in the ayurvedic system of medicine.ObjectiveIn the present study, we have evaluated the antiproliferative activity of a standardized W. somnifera root extract (Viwithan) against different human and murine cancer cell lines.Materials and methodsThe cytotoxicity of Viwithan was determined using thiazolyl blue tetrazolium blue assay and crystal violet staining. The apoptotic changes in B16F1 cells following treatment with Viwithan were observed by acridine orange/ethidium bromide (AO/EB) staining and DNA fragmentation assay. The binding affinity of withanolides in Viwithan with antiapoptotic proteins B-cell lymphoma 2, B-cell lymphoma-extra large, and myeloid cell leukemia 1 (MCL-1) were studied using in silico approach.ResultsThe half maximal inhibitory concentration (IC50) values of Viwithan against liver hepatocellular carcinoma, Henrietta Lacks cervical carcinoma cells, human colorectal carcinoma cell line, and Ehrlich ascites carcinoma cells were 1830, 968, 2715, and 633 μg/ml, respectively. Interestingly, Viwithan was highly effective against B16F1 cells with an IC50 value of 220 μg/ml after 24 h treatment. The morphological alterations of apoptotic cell death were clearly observed in the AO/EB-stained cells after treatment with Viwithan. Viwithan induced late apoptotic changes in treated B16F1 cells as evident by the ladder formation of fragmented DNA in a time-dependent manner. The findings of molecular docking showed that withanolides present in Viwithan have a more binding affinity with the antiapoptotic proteins, particularly MCL-1.ConclusionWe have reported for the first time that Viwithan with 5% withanolides has a potent cytotoxic effect, particularly against B16F1 murine melanoma cells among the different cancer cell lines tested.SummaryThe present study reports for the first time that Viwithan, a standardized 5% Withania somnifera root extract, has potent cytotoxicity against B16F1 murine melanoma cellsWe have investigated the in vitro cytotoxicity of Viwithan in different human and murine cancer cells. Interestingly, we found that Viwithan was particularly very effective against B16F1 melanoma cells with a half maximal inhibitory concentration value of 220 μg/mlThe microscopic observations following acridine orange/ethidium bromide staining and DNA fragmentation assays clearly indicated that Viwithan might initiate late apoptosis in B16F1 cellsThe binding affinity of withanolides in Viwithan with antiapoptotic proteins of B-cell lymphoma 2 family was predicted using AutoDock tool. The results from in silico studies indicated a plausible synergistic effect of withanolides attributing to the Viwithan-induced apoptosis through suppression of intrinsic pathway for carcinogenesis. Abbreviations used: MTT: Thiazolyl blue tetrazolium blue; DMSO: Dimethyl sulfoxide; BSA: Bovine serum albumin; DMEM: Dulbecco's minimum essential medium; NCCS: National Centre for Cell Science; PBS: Phosphate-Buffered Saline; HepG2: Liver hepatocellular carcinoma; HeLa: Henrietta Lacks cervical carcinoma cells; HCT-116: Human colorectal carcinoma cell line; EAC: Ehrlich ascites carcinoma cells; IC50: Half maximal inhibitory concentration; AO/EB: Acridine orange/Ethidium bromide; BCL-2: B-cell lymphoma 2; BCL-XL: B-cell lymphoma-extra large; MCL-1: Myeloid cell leukemia 1; PDB: Protein Data Bank; ANOVA: Analysis of variance.

Dataset Information

Solanum incanum extract (SR-T100) induces melanoma cell apoptosis and inhibits established lung metastasis.

Publications

<i>Solanum incanum</i> extract (SR-T100) induces melanoma cell apoptosis and inhibits established lung metastasis.

Similar Datasets

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