Piperine Targets Different Drug Resistance Mechanisms in Human Ovarian Cancer Cell Lines Leading to Increased Sensitivity to Cytotoxic Drugs

Karolina Wojtowicz,Michał Nowicki,Karolina Sterzyńska,Radosław Januchowski,Monika Świerczewska,Maciej Zabel

doi:10.3390/ijms22084243

Abstract

Our goal was to examine the anticancer effects of piperine against the resistant human ovarian cancer cells and to explore the molecular mechanisms responsible for its anticancer effects. Our study used drug-sensitive ovarian cancer cell line W1 and its sublines resistant to paclitaxel (PAC) and topotecan (TOP). We analyzed the cytotoxic effect of piperine and cytostatic drugs using an MTT assay. The impact of piperine on protein expression was determined by immunofluorescence and Western blot. We also examined its effect on cell proliferation and migration. We noticed a different level of piperine resistance between cell lines. Piperine increases the cytotoxic effect of PAC and TOP in drug-resistant cells. We observed an increase in PTPRK expression correlated with decreased pTYR level after piperine treatment and downregulation of P-gp and BCRP expression. We also noted a decrease in COL3A1 and TGFBI expression in investigated cell lines and increased COL3A1 expression in media from W1PR2 cells. The expression of Ki67 protein and cell proliferation rate decreased after piperine treatment. Piperine markedly inhibited W1TR cell migration. Piperine can be considered a potential anticancer agent that can increase chemotherapy effectiveness in cancer patients.

Highlights

Ovarian cancer is a heterogeneous malignancy with variable clinical development that remains the most challenging disease in gynecologic oncology [1,2]
Our findings suggest that piperine targets different drug resistance mechanisms and may potentially be a therapeutic agent for preventing and treating ovarian cancer
We looked through the literature data, but we did not find any relation between piperine and COL3A1 or other extracellular matrix proteins (ECM) components

Summary

Introduction

Ovarian cancer is a heterogeneous malignancy with variable clinical development that remains the most challenging disease in gynecologic oncology [1,2]. Most ovarian cancer patients are diagnosed in advanced stages (III or IV according to FIGO classification). The prognosis of ovarian cancer is directly related to the stage of tumor and tumor cells remaining after resection [3]. Surgical resection along with platinum-based chemotherapy is a standard treatment option for ovarian cancer. Patients undergo the platinum/taxane treatment as the first-line chemotherapeutic modality [4,5].

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