Determination of Combined Effect of pH and Withania somnifera on Human Breast Cancer Cell Line MDAMB- 231

Background: The intratumor microenvironment is intrinsically acidic due to accumulation of lactic acid as a result of increased aerobic and anaerobic glycolysis by the tumor cells. In general, the extracellular pH (pHe) in human tumors is below 7.0, whereas the intracellular pH (pHi) is maintained at neutral range, i.e., >7.0, by powerful pHi control mechanisms. The low pHe and the significant gradients between pHe and pHi affect markedly the response of tumors to various treatments such as chemotherapy, radiotherapy and hyperthermia. Methods: In the present study, the effect of alkaline pH on human breast cancer cell line MDA-MB231 was investigated in presence of methanolic extract of Ashwagandha (Withania somnifera) in 10% DMSO at the rate of 50 μg/ml. Results: It was found that alkaline pH caused an increase in the cytotoxic effect of Withania somnifera on MDA-MB-231 cells by approximately ten folds. Conclusion: The alkaline pHe caused an increase in the cellular uptake of Withania extract and thus increased its overall cytotoxicity. Better understanding of the control mechanisms of pHe and pHi in tumors may lead to device effective treatment strategy of human tumors.