Effects of Withania somnifera and Tinospora cordifolia extracts on the side population phenotype of human epithelial cancer cells: toward targeting multidrug resistance in cancer
Maliyakkal N, Appadath Beeran A, Balaji SA, Udupa N, Ranganath Pai S, Rangarajan A
Integrative cancer therapies · 14 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- In vitro/mechanistic study (classified by our AI screen)
- Studied in
- Cells or lab samples
- Main outcome
- Mechanisms only
Who paid for it
- Funding
- Independent funding
- University or hospital
- Indian Institute of Science
- Government
- Department of Biotechnology, Ministry of Science and Technology, India
- Government
- Department of Science and Technology, Ministry of Science and Technology, India
- Nonprofit
- The Wellcome Trust DBT India Alliance
Based on 4 listed funder(s).
Publication
- Published
- 2014-12-29 · Integr Cancer Ther · vol. 14 · issue 2 · pp. 156–171
- Publisher
- SAGE Publishing
- Cited
- 19 citations · more than 73% of similar papers · 0.9× the field average
- References
- 43 works
- Access
- Open access (journal)
- Research areas
- Cancer Cells and Metastasis · Phytochemicals and Medicinal Plants · Pluripotent Stem Cells Research
- Keywords
- Tinospora cordifolia, Cancer stem cell, Side population, Efflux, Cancer, Population, Cancer cell, Withania somnifera, Phenotype, Pharmacology, Cytotoxicity, Biology, Stem cell, Cancer research, Chemistry, Traditional medicine, Medicine, In vitro, Biochemistry, Cell biology, Pathology, Gene, Genetics
- MeSH
- cell line, tumor, humans, tinospora, withania, neoplasms, glandular and epithelial, plant extracts, antineoplastic agents, phytogenic, solvents, medicine, ayurvedic, flow cytometry, drug resistance, multiple, dose-response relationship, drug, drug resistance, neoplasm, phenotype, neoplastic stem cells
6 authors
From IN
- Naseer MaliyakkalManipal Academy of Higher Education; Manipal Hospital; Indian Institute of Science Bangalore
- Asmy Appadath BeeranManipal Academy of Higher Education
- Sai A. BalajiIndian Institute of Science Bangalore
- N UdupaManipal Academy of Higher Education
- K. Sreedhara Ranganath PaiManipal Academy of Higher Education
- Annapoorni RangarajanIndian Institute of Science Bangalore
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.
Abstract via Europe PMC. Copyright remains with the authors or publisher.
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