PIPERINE IN THE PREVENTION OF THE DECREASED TAMOXIFEN SENSITIVITY IN MCF-7 BREAST CANCER CELL LINE

Authors

  • Sandy Vitria Kurniawan Biomedical Sciences Postgraduate Program, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia. Department of Pharmacology and Pharmacy, Faculty of Medicine, Atma Jaya Catholic University, Jakarta 12930, Indonesia
  • Lies Sugiarti Biomedical Sciences Postgraduate Program, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia.
  • Septelia Inawati Wanandi Department of Biochemistry and Molecular Biology, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia.
  • Melva Louisa Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia.

DOI:

https://doi.org/10.22159/ijap.2018.v10s1.74

Keywords:

P-glycoprotein, Piperine, Tamoxifen

Abstract

Objective: This study was designed to analyze the role of piperine in modulating P-glycoprotein mRNA expression when added in combination with
tamoxifen 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-glycoprotein
inhibitor positive control) for up to 12 days. We assessed the cell viability and isolated total RNA from them. We quantified P-glycoprotein expressions
using 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 shown
to be dose dependent.
Conclusion: Piperine prevents the development of breast cancer cell tamoxifen resistance, probably through its inhibition of P-glycoprotein expression.

Downloads

Download data is not yet available.

References

Global Burden of Disease Cancer Collaboration, Fitzmaurice C,

Allen C, Barber RM, Barregard L, Bhutta ZA, et al. Global, regional,

and national cancer incidence, mortality, years of life lost, years lived

with disability, and disability-adjusted life-years for 32 cancer groups,

to 2015: A systematic analysis for the global burden of disease

study. JAMA Oncol 2017;3:524-48.

Apuri S. Neoadjuvant and adjuvant therapies for breast cancer. South

Med J 2017;110:638-42.

Nabholtz JM, Buzdar A, Pollak M, Harwin W, Burton G, Mangalik A,

et al. Anastrozole is superior to tamoxifen as first-line therapy for

advanced breast cancer in postmenopausal women: Results of a North

American multicenter randomized trial. Arimidex study group. J Clin

Oncol 2000;18:3758-67.

Mouridsen H, Gershanovich M, Sun Y, Pérez-Carrión R, Boni C,

Monnier A, et al. Superior efficacy of letrozole versus tamoxifen as

first-line therapy for postmenopausal women with advanced breast

cancer: Results of a Phase III study of the international letrozole breast

cancer group. J Clin Oncol 2001;19:2596-606.

Eckford PD, Sharom FJ. ABC efflux pump-based resistance to

chemotherapy drugs. Chem Rev 2009;109:2989-3011.

Harmsen S, Meijerman I, Febus CL, Maas-Bakker RF, Beijnen JH,

Schellens JH, et al. PXR-mediated induction of P-glycoprotein by

anticancer drugs in a human colon adenocarcinoma-derived cell line.

Cancer Chemother Pharmacol 2010;66:765-71.

Amin ML. P-glycoprotein inhibition for optimal drug delivery. Drug

Target Insights 2013;7:27-34.

Bansal T, Jaggi M, Khar RK, Talegaonkar S. Emerging significance

of flavonoids as P-glycoprotein inhibitors in cancer chemotherapy.

J Pharm Pharm Sci 2009;12:46-78.

Abdallah HM, Al-Abd AM, El-Dine RS, El-Halawany AM.

P-glycoprotein inhibitors of natural origin as potential tumor chemosensitizers:

A review. J Adv Res 2015;6:45-62.

Aher S, Biradar S, Gopu CL, Paradkar A. Novel pepper extract

for enhanced P-glycoprotein inhibition. J Pharm Pharmacol

;61:1179-86.

Singh A, Duggal S. Piperine-review of advances in pharmacology. Int J

Pharm Sci Nanotech 2009;2:615-20.

Louisa M, Sugiarti L, Kurniawan SV, Wanandi SI. Curcumin increases

anti-cancer activity of tamoxifen in MCF-7 breast cancer cells

through the suppression of MDR1 mRNA expression. Adv Sci Lett

;23:6838-40.

Livak KJ, Schmittgen TD. Analysis of relative gene expression data

using real-time quantitative PCR and the 2(-delta delta C(T)) method.

Methods 2001;25:402-8.

Yang K, Wu J, Li X. Recent advances in the research of P-glycoprotein

inhibitors. Biosci Trends 2008;2:137-46.

Lykkesfeldt AE, Madsen MW, Briand P. Altered expression of

estrogen-regulated genes in a tamoxifen-resistant and ICI 164,384 and

ICI 182,780 sensitive human breast cancer cell line, MCF-7/TAMR-1.

Cancer Res 1994;54:1587-95.

Lin JH. Drug-drug interaction mediated by inhibition and induction of P-glycoprotein. Adv Drug Deliv Rev 2003;55:53-81.

Purushothaman A, Nandhakumar E, Sachdanandam P. Anticancer effect

of shemamruthaa (a phytochemical formulation) on 7, 12-dimethybenz

(a) anthracene induced mammary carcinoma in rats. Asian J Pharm Clin

Res 2012;5:101-7.

Tapadiya G, Metku M, Deokate U, Khadabadi S, Saboo S, Sahu K.

Quantitatives estimation of piperine from pharmaceutical dosage form

by HPTLC. Asian J Pharm Clin Res 2009;2:47-50.

Patel S, Vyas N. Validated spectrofluorimetric method for estimation of

piperine in an ayurvedic formulation. Asian J Pharm Clin Res 2012;5:231-3.

Callaghan R, Higgins CF. Interaction of tamoxifen with the multidrug

resistance P-glycoprotein. Br J Cancer 1995;71:294-9.

Li S, Lei Y, Jia Y, Li N, Wink M, Ma Y, et al. Piperine, a piperidine

alkaloid from Piper nigrum re-sensitizes P-gp, MRP1 and BCRP

dependent multidrug resistant cancer cells. Phytomedicine

;19:83-7.

Bhardwaj RK, Glaeser H, Becquemont L, Klotz U, Gupta SK, Fromm MF,

et al. Piperine, a major constituent of black pepper, inhibits human

P-glycoprotein and CYP3A4. J Pharmacol Exp Ther 2002;302:645-50.

Han Y, Chin Tan TM, Lim LY. In vitro and in vivo evaluation of the

effects of piperine on P-gp function and expression. Toxicol Appl

Pharmacol 2008;230:283-9.

Beck WT, Grogan TM, Willman CL, Cordon-Cardo C, Parham DM,

Kuttesch JF, et al. Methods to detect P-glycoprotein-associated

multidrug resistance in patients’ tumors: Consensus recommendations.

Cancer Res 1996;56:3010-20.

Published

20-12-2018

How to Cite

Kurniawan, S. V., Sugiarti, L., Wanandi, S. I., & Louisa, M. (2018). PIPERINE IN THE PREVENTION OF THE DECREASED TAMOXIFEN SENSITIVITY IN MCF-7 BREAST CANCER CELL LINE. International Journal of Applied Pharmaceutics, 10(1), 335–337. https://doi.org/10.22159/ijap.2018.v10s1.74

Issue

Section

Original Article(s)