title: The enriched fraction of Vernonia cinerea L. induces apoptosis and inhibits multi-drug resistance transporters in human epithelial cancer cells.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka, India.
authors.forename: Asmy
authors.initials: A
authors.lastname: Appadath Beeran
authors.affiliation: Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka, India.
authors.forename: Naseer
authors.initials: N
authors.lastname: Maliyakkal
authors.affiliation: Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka, India.
authors.forename: Chamallamudi Mallikarjuna
authors.initials: CM
authors.lastname: Rao
authors.affiliation: Department of Pharmacy Management, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka, India. Electronic address: n.udupa@manipal.edu.
authors.forename: Nayanabhirama
authors.initials: N
authors.lastname: Udupa
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D006367:HeLa Cells; D006801:Humans; D007194:India; D061986:MCF-7 Cells; D008515:Medicine, Ayurvedic; D026901:Membrane Transport Proteins / Q000378:metabolism; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy / Q000473:pathology; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D035741:Vernonia / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D026901:Membrane Transport Proteins; D010936:Plant Extracts
keywords: Anti-cancer; Apoptosis; Cytotoxicity; Multi-drug resistance (MDR); Vernonia cinerea L.