The enriched fraction of Vernonia cinerea L. induces apoptosis and inhibits multi-drug resistance transporters in human epithelial cancer cells

Beeran, Asmy Appadath and Maliyakkal, Naseer and Rao, Mallikarjuna C and Udupa, N (2014) The enriched fraction of Vernonia cinerea L. induces apoptosis and inhibits multi-drug resistance transporters in human epithelial cancer cells. Journal of Ethnopharmacology, 158. pp. 33-42. ISSN 0378-8741

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Abstract

Ethnopharmacological relevance: Vernonia cinerea Less. (VC) of the family Asteraceaes is considered as the sacred plant; ‘Dasapushpam’ which is ethnopharmacologically significant to the people of Kerala in India. In fact, VC has been used in the traditional system of medicine (Ayurveda) for the treatment of various ailments including cancer. Materials and methods: Cytotoxicity of the ethanolic extract of VC (VC-ET), petroleum ether fraction (VC-PET), dichloromethane fraction (VC-DCM), n-butyl alcohol fraction (VC-BT), and rest fraction (VC-R) was evaluated in cervical carcinoma (HeLa), lung adenocarcinoma (A549), breast cancer (MCF-7), and colon carcinoma (Caco-2) cells using Sulforhodamine B (SRB) assay. The apoptotic effects of VC-DCM were assessed in cancer cells using Annexin V assay. The effects of VC-DCM on multi-drug resistance (MDR) transporters in HeLa, A549, MCF-7, and Caco-2 cells were evaluated using flow cytometry based functional assays. Similarly, drug uptake in cancer cells and sensitization of cancer cells towards chemotherapeutic drugs in the presence of VC-DCM were studied using Daunorubicin (DNR) accumulation assay and SRB assay, respectively. Results:Cytotoxicity assay revealed that the enriched fraction of VC (VC-DCM) possessed dose-dependent cytotoxic effects in human epithelial cancer cells (HeLa, A549, MCF-7, and Caco-2). Further, treatment of cancer cells (HeLa, A549, MCF-7, and Caco-2) with VC-DCM led to a significant increase in both early and late apoptosis, indicating the induction of apoptosis. Interestingly, VC-DCM significantly inhibited functional activity of MDR transporters (ABC-B1 and ABC-G2), enhanced DNR-uptake in cancer cells, and sensitized cancer cells towards chemotherapeutic drug-mediated cytotoxicity, thus indicating the ability of VC-DCM to reverse MDR in cancer and enhance the cytotoxic effects of anticancer drugs. Conclusions:A methodological investigation on the anti-cancer properties of Vernonia cinerea Less. (VC) revealed that an enriched fraction of VC (VC-DCM) possessed cytotoxic effects, triggered apoptosis, inhibited MDR transporters, enhanced drug uptake, and sensitized cancer cells towards anticancer drug-mediated cytotoxicity in human epithelial cancer cells. Thus, VC appears to be promising for an effective treatment of various drug-resistant human epithelial cancers.

Item Type: Article
Uncontrolled Keywords: Vernonia cinerea L;anti-cancer; cytotoxicity; apoptosis; multi-drug resistance(MDR
Subjects: Pharmacy > MCOPS Manipal > Pharmacology
Pharmacy > MCOPS Manipal > Pharmacy Management
Depositing User: KMC Manipal
Date Deposited: 13 Nov 2014 04:13
Last Modified: 13 Nov 2014 04:13
URI: http://eprints.manipal.edu/id/eprint/141057

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