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

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 top...

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Main Authors: Karolina Wojtowicz, Karolina Sterzyńska, Monika Świerczewska, Michał Nowicki, Maciej Zabel, Radosław Januchowski
Format: Article
Language:English
Published: MDPI AG 2021-04-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/8/4243
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author Karolina Wojtowicz
Karolina Sterzyńska
Monika Świerczewska
Michał Nowicki
Maciej Zabel
Radosław Januchowski
author_facet Karolina Wojtowicz
Karolina Sterzyńska
Monika Świerczewska
Michał Nowicki
Maciej Zabel
Radosław Januchowski
author_sort Karolina Wojtowicz
collection DOAJ
description 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.
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spelling doaj.art-bce1afed4faa4879a1393d8db2b539f02023-11-21T16:14:45ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-04-01228424310.3390/ijms22084243Piperine Targets Different Drug Resistance Mechanisms in Human Ovarian Cancer Cell Lines Leading to Increased Sensitivity to Cytotoxic DrugsKarolina Wojtowicz0Karolina Sterzyńska1Monika Świerczewska2Michał Nowicki3Maciej Zabel4Radosław Januchowski5Department of Histology and Embryology, Poznań University of Medical Sciences, Święcickiego 6 St., 61-781 Poznań, PolandDepartment of Histology and Embryology, Poznań University of Medical Sciences, Święcickiego 6 St., 61-781 Poznań, PolandDepartment of Histology and Embryology, Poznań University of Medical Sciences, Święcickiego 6 St., 61-781 Poznań, PolandDepartment of Histology and Embryology, Poznań University of Medical Sciences, Święcickiego 6 St., 61-781 Poznań, PolandDepartment of Anatomy and Histology, Collegium Medicum, University of Zielona Gora, Zyty 28 St., 65-046 Zielona Gora, PolandDepartment of Anatomy and Histology, Collegium Medicum, University of Zielona Gora, Zyty 28 St., 65-046 Zielona Gora, PolandOur 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.https://www.mdpi.com/1422-0067/22/8/4243ovarian cancerpiperinedrug resistanceprotein phosphorylationdrug transporterscancer stem cells
spellingShingle Karolina Wojtowicz
Karolina Sterzyńska
Monika Świerczewska
Michał Nowicki
Maciej Zabel
Radosław Januchowski
Piperine Targets Different Drug Resistance Mechanisms in Human Ovarian Cancer Cell Lines Leading to Increased Sensitivity to Cytotoxic Drugs
International Journal of Molecular Sciences
ovarian cancer
piperine
drug resistance
protein phosphorylation
drug transporters
cancer stem cells
title Piperine Targets Different Drug Resistance Mechanisms in Human Ovarian Cancer Cell Lines Leading to Increased Sensitivity to Cytotoxic Drugs
title_full Piperine Targets Different Drug Resistance Mechanisms in Human Ovarian Cancer Cell Lines Leading to Increased Sensitivity to Cytotoxic Drugs
title_fullStr Piperine Targets Different Drug Resistance Mechanisms in Human Ovarian Cancer Cell Lines Leading to Increased Sensitivity to Cytotoxic Drugs
title_full_unstemmed Piperine Targets Different Drug Resistance Mechanisms in Human Ovarian Cancer Cell Lines Leading to Increased Sensitivity to Cytotoxic Drugs
title_short Piperine Targets Different Drug Resistance Mechanisms in Human Ovarian Cancer Cell Lines Leading to Increased Sensitivity to Cytotoxic Drugs
title_sort piperine targets different drug resistance mechanisms in human ovarian cancer cell lines leading to increased sensitivity to cytotoxic drugs
topic ovarian cancer
piperine
drug resistance
protein phosphorylation
drug transporters
cancer stem cells
url https://www.mdpi.com/1422-0067/22/8/4243
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