Maliyakkal, Naseer and Beeran, Asmy Appadath and Balaji, Sai A and Udupa, Nayanabhirama and Pai, Sreedhara Ranganath and Rangarajan, Annapoorni (2015) Effects of Withania somnifera and Tinospora cordifolia Extracts on the Side Population Phenotype of Human Epithelial Cancer Cells: Toward Targeting Multidrug Resistance in Cancer. In: INTEGRATIVE CANCER THERAPIES, 14 (2). pp. 156-171.
Full text not available from this repository. (Request a copy)Abstract
Recent reports suggest the existence of a subpopulation of stem-like cancer cells, termed as cancer stem cells (CSCs), which bear functional and phenotypic resemblance with the adult, tissue-resident stem cells. Side population (SP) assay based on differential efflux of Hoechst 33342 has been effectively used for the isolation of CSCs. The drug resistance properties of SP cells are typically due to the increased expression of ABC transporters leading to drug efflux. Conventionally used chemotherapeutic drugs may often leads to an enrichment of SP, revealing their inability to target the drug-resistant SP and CSCs. Thus, identification of agents that can reduce the SP phenotype is currently in vogue in cancer therapeutics. Withania somnifera (WS) and Tinospora cordifolia (TC) have been used in Ayurveda for treating various diseases, including cancer. In the current study, we have investigated the effects of ethanolic (ET) extracts of WS and TC on the cancer SP phenotype. Interestingly, we found significant decrease in SP on treatment with TC-ET, but not with WS-ET. The SP-inhibitory TC-ET was further fractionated into petroleum ether (TC-PET), dichloromethane (TC-DCM), and n-butyl alcohol (TC-nBT) fractions using bioactivity-guided fractionation. Our data revealed that TC-PET and TC-DCM, but not TC-nBT, significantly inhibited SP in a dose-dependent manner. Furthermore, flow cytometry-based functional assays revealed that TC-PET and TC-DCM significantly inhibited ABC-B1 and ABC-G2 transporters and sensitized cancer cells toward chemotherapeutic drug-mediated cytotoxicity. Thus, the TC-PET and TC-DCM may harbor phytochemicals with the potential to reverse the drug-resistant phenotype, thus improving the efficacy of cancer chemotherapy.
| Item Type: | Journal Article |
|---|---|
| Publication: | INTEGRATIVE CANCER THERAPIES |
| Publisher: | SAGE PUBLICATIONS INC |
| Keywords: | cancer stem-like cells; multidrug resistance; side population; Withania somnifera; Tinospora cordifolia |
| Department/Centre: | Division of Biological Sciences > Molecular Reproduction, Development & Genetics |
| Date Deposited: | 01 Apr 2015 12:08 |
| Last Modified: | 01 Apr 2015 12:08 |
| URI: | http://eprints.iisc.ac.in/id/eprint/51126 |
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