Abstract
Objective: This study was designed to analyze the role of piperine in modulating P-glycoprotein mRNA expression when added in combination withtamoxifen to breast cancer cells in culture.Methods: MCF-7 breast cancer cells were treated with 1 μM tamoxifen with or without piperine (12.5, 25, or 50 μM) or verapamil 50 μM (P-glycoproteininhibitor positive control) for up to 12 days. We assessed the cell viability and isolated total RNA from them. We quantified P-glycoprotein expressionsusing quantitative reverse transcription polymerase chain reaction.Results: Administration of various doses of piperine decreased MCF-7 breast cancer cell viability. Piperine, when given in combination with tamoxifen,decreased the expression of P-glycoprotein mRNA in cells compared with the expression in cells treated with tamoxifen only. The effects were shownto be dose dependent.Conclusion: Piperine prevents the development of breast cancer cell tamoxifen resistance, probably through its inhibition of P-glycoprotein expression.
Highlights
Breast cancer continues to be a global burden for women as the most common cancer and the leading cause of cancer deaths in women [1]
The analysis of P-glycoprotein mRNA expressions after treatment of MCF-7 cells with tamoxifen (1 μM) showed a similar trend to that in the cell viability curve, increasing in a time-dependent manner starting on day 6 (Fig. 2)
We found decreased P-glycoprotein mRNA expressions after the concomitant treatment of MCF-7 cells with tamoxifen (1 μM) and either piperine (12.5, 25, and 50 μM) or verapamil (50 μM) (Fig. 4)
Summary
Breast cancer continues to be a global burden for women as the most common cancer and the leading cause of cancer deaths in women [1]. Premenopausal women with estrogen-positive type of breast cancer can benefit from tamoxifen treatment [2]. Studies have shown that the response rates to tamoxifen are approximately 17–33% with times to progression between 5 and 8.3 months [3,4]. The long-term use of tamoxifen has been shown to induce decreased cancer cell sensitivity to the drug; one mechanism of resistance is the increased expression of drug efflux transporters such as P-glycoprotein [5]. P-glycoprotein mediates resistance to various anticancer drugs, such as tamoxifen, vincristine, vinblastine, and paclitaxel. The long-term use of anticancer drugs can trigger increased P-glycoprotein expression through the activation of pregnane X receptor (PXR) so that the anticancer drugs cannot attain effective concentrations inside the cells, leading to drug treatment failure [6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
