Enhancement of paclitaxel and doxorubicin cytotoxicity in breast cancer cell lines in combination with piperine treatment and analysis of expression of autophagy and apoptosis genes

Pushpa Ragini S, Naga Divya AV, Anusha Ch, Kanthaiah YV

Pdf Page Numbers :- 62-67

 Pushpa Ragini S¹, Srinivasa Rao B¹, Naga Divya AV¹, Anusha Ch¹ and Kanthaiah YV^1,*

¹KIMS Foundation and Research Centre, Minister Road, Secunderabad - 500003, AP., India.

*Corresponding author: Dr. YV. Kanthaiah, KIMS Foundation and Research Centre, Minister Road, Secunderabad - 500003, AP, India. Email: kantha10@yahoo.com

Received 10 February 2014; Revised 24 March 2014; Accepted 31 March 2014

Citation: Pushpa Ragini S, Naga Divya AV, Anusha Ch, Kanthaiah YV (2014) Enhancement of paclitaxel and doxorubicin cytotoxicity in breast cancer cell lines in combination with piperine treatment and analysis of expression of autophagy and apoptosis genes. J Med Sci Res 2(2):62-67. DOI: http://dx.doi.org/10.17727/JMSR.2014/2-012  

Copyright: © 2014 Pushpa Ragini S et al. Published by KIMS Foundation and Research Center. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Abstract

Background: Breast cancer treatment failure mainly attributed to drug resistance and suboptimal dosage of drugs reaching to the actual target. Several Bioenhancers have been used for enhancing drug availability to the target cancer cells in sustainable manner. Piperine is one such molecule has been used for increasing serum drug concentrations by enhancing the drug absorption in the stomach. However it is not clear whether piperine will have direct effect on cells when used along with drugs. In the present study we have studied the direct effect of piperine in combination with Doxorubicin and paclitaxel.

Methodology: MDA MB -231 cell lines were cultured and treated with different concentrations of paclitaxel and Doxorubicin. The piperine at 25 µM was added to all drug concentrations. Induction of cytotoxic effect of doxorubicin and paclitaxel in combination with piperine was analysed by MTT cytotoxic assay, CFSE cell proliferation assay. Further the apoptotic and autophagy genes i.e. Beclin 1, P21, Bax and Survivin expression were analysed by semi quantitative RT PCR.

Results: Piperine enhanced the cytotoxicity effect of doxorubicin and paclitaxel at all concentrations of drugs. Piperine alone did not cause cytotoxicity or inhibition of cell proliferation. However piperine enhanced the cytotoxic and anti proliferative effect of paclitaxel and doxorubicin when used in combination. Further, piperine in combination with drugs shown to induce P21 expression and reduce surviving expression. We have not observed changes in Beclin 1 and Bax genes expression with either drugs alone or in piperine combination.

Conclusion: Piperine has increased the cytotoxic and anti proliferative affects of doxorubicin and Paclitaxel drugs when used directly in cell lines. However the molecular mechanism has to be further analysed to understand the actual mode of action of piperine in breast cancer cells.

Keywords: Breast cancer; Piperine; MDA MB -231; Paclitaxel; Doxorubicin