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

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 antibreast 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.

Thymoquinone, piperine, and sorafenib combinations attenuate liver and breast cancers progression: epigenetic and molecular docking approaches

“…Moreover, TQ synergistically improved the anticancer activity of doxorubicin and cisplatin in hepatocellular carcinoma HepG2 cells [ 45 ]. Similarly, PIP was also reported to exert chemo-modulatory effects on chemotherapeutic drugs in different cancers [ 46 , 47 ].…”

“…Impaired apoptosis is reported as one of the mechanisms leading to SOR resistance in cancer cells and the antiapoptotic protein, B-cell lymphoma 2, is suggested to modulate this phenomenon [ 50 ]. Many reports have attributed the anticancer effects of TQ and PIP to its selective proapoptotic actions through the regulation of p53, Bcl-2-associated X protein, and B-cell lymphoma 2 equilibrium and activation of the caspase enzymes [ 46 , 56 ]. We have examined the apoptotic and necrotic cell death after individual and combined TQ, PIP, and SOR treatment.…”

Targeted Anticancer Drug Delivery Using Chitosan, Carbon Quantum Dots, and Aptamers to Deliver Ganoderic Acid and 5‐Fluorouracil

“…In the end, 5 μl of Annexin V‐fluorescein isothiocyanate (FITC) and 5 μl of Propidium Iodide were added to the cell suspension. After the mixture was left to sit in the dark for 15 min, the findings were evaluated using a flow cytometer (BD Biosciences, USA) [64] …”

“…After the mixture was left to sit in the dark for 15 min, the findings were evaluated using a flow cytometer (BD Biosciences, USA). [64]…”

Secondary Metabolites of Soil Actinomycetes, UTMC 676 and UTMC 919, Induces Apoptosis in Human Non‑Small-Cell Lung Cancer Cell Line

“…These compounds often induce apoptosis and suppress metastasis, inhibiting cancer growth and development (9,10). Many studies have suggested that chemotherapeutic drugs-caused cell death may involve mitochondrial pathway-derived apoptosis (11)(12)(13).…”