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. 2021 May;50(5):1037-1047.
doi: 10.18502/ijph.v50i5.6121.

The Synergistic Combination of Cisplatin and Piperine Induces Apoptosis in MCF-7 Cell Line

Abolfazl Fattah  1 , Ali Morovati  2 , Zahra Niknam  3 , Ladan Mashouri  4 , Amirhooman Asadi  5 , Shirin Tvangar Rizi  6 , Mojtaba Abbasi  7   8 , Fatemeh Shakeri  9 , Omid Abazari  10
Affiliations

The Synergistic Combination of Cisplatin and Piperine Induces Apoptosis in MCF-7 Cell Line

Abolfazl Fattah et al. Iran J Public Health. 2021 May.

Abstract

Background: Piperine is a natural compound obtained from the Piper nigrum that exhibits anti-proliferative and anti-cancer activity in cancer cell lines. We analyzed the cytotoxic effect of piperine combined with cisplatin compound in the human MCF-7 breast cancer cell line and the underlying mechanism.

Methods: The present in vitro study was performed on MCF-7 cell line in Jahrom University of Medical Sciences between, Jahrom, Iran from 2016 to 2017. Cultured MCF-7 cells were seeded into four groups: a control group (untreated group), a group treated with cisplatin, a group treated with piperine and a group treated with cisplatin and piperine. Cell viability was analyzed using the MTT assay method. Flow c-ytometric analysis was investigated for apoptosis. The mRNA and protein expression of the apoptotic regulators p53, Bcl-2, Bax, caspase 3 and caspase 9 were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analysis.

Results: Piperine (20 and 30 μM) in combination with cisplatin (5, 10 and 15 μM) for 24 h synergistically inhibited cell viability of MCF-7 breast cancer cells more than piperine and cisplatin used alone. Synergistic anti-breast cancer activities cisplatin (5 μM) and piperine (20 μM) were via inducing apoptosis. Piperine (20 μM) and cisplatin (5 μM) for 24 h induce apoptosis strongly through reduction of Bcl-2 and increase of caspase 3, p53, caspase 9, and Bax.

Conclusion: Piperine in combination with cisplatin could trigger p53-mediated apoptosis more effective than cisplatin alone in MCF-7 breast cancer cells, reducing the toxic dose of cisplatin used in cancer chemotherapy.

Keywords: Apoptosis; Breast cancer; Caspase; Cisplatin; Piperine.

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Conflict of interest statement

Conflict of interest The authors declare that there is no conflict of interest.

Figures

Fig. 1:
Fig. 1:
Inhibition effect of (A) piperine, (B) cisplatin, and (C) their combination on cell viability of human Breast cancer MCF-7 cells. *P<0.05, **P<0.01 and ***P<0.001 compared with the untreated group
Fig. 2:
Fig. 2:
The effect of piperine, cisplatin and their combination on apoptosis of human breast cancer MCF-7 cells. The image of flow cytometric analysis indicating necrotic cells (Q1), late apoptotic cells (Q2), early apoptotic cells (Q3) and viable cells (Q4)
Fig. 3:
Fig. 3:
The effect of piperine, cisplatin and their combined treatment on (A) P53, (B) Bax, and (C) Bcl-2 protein expression. *P<0.05 and **P<0.01 compared with the control group
Fig. 4:
Fig. 4:
The mRNA expression of A) Caspase-3 and B) Caspase-9 after treatment of piperine, cisplatin, and their combination were analyzed with qRT-PCR. *P<0.05 and **P<0.01 compared to the control group
See this image and copyright information in PMC

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