Docetaxel Regulates the Interaction of p53 with MDM2 and Sin3A to Suppress MCF-7 Breast Cancer Cells

Authors

Keywords:

Apoptosis,, Cancer, Chemotherapy, Docetaxel, MDM2

Abstract

Docetaxel is one of the most actively used chemotherapeutic agent in breast cancer which is the most frequent tumor in women. Recent studies propose that blocking the p53-MDM2 interaction may be effective in cancer treatment while the Sin3A mutation enhances cell proliferation in estrogen receptor (ER)-positive breast cancers. We aimed to investigate the effects of docetaxel on gene expression interactions and apoptosis in ER-positive breast cancer cell lines (MCF-7). MCF-7 cells were incubated for 24h with the treatment of escalating molar concentrations of docetaxel. The p53, MDM2 and Sin3A gene expression levels were measured by Real-Time PCR. The MTT assay was used to determine cellular viability. Apoptotic cells were detected by TUNEL. The mRNA expressions of p53, MDM2, and Sin3A increased in the same dose-dependent manner suggesting the highest effective level is 100nM docetaxel concentration (p<0.001). The p53 expression levels were strongly correlated with MDM2 (r=0.9379; p<10-7) and Sin3A (r=0.9965; p<10-13) in untreated, 10nM, 100nM and 1µM docetaxel concentrations. Cell viability of MCF-7 cells decreased dramatically in the 10µM and 100µM docetaxel treatments (p<0.001) and the IC50 value was 10µM. Apoptotic cell density was enhanced with the treatments of 10nM, 100nM, and 1µM docetaxel (p<0.001) in response to the gene expression levels. Our findings suggest that docetaxel directs the MCF-7 breast cancer cells to apoptosis in a dose-dependent manner and may thus further regulate the interaction of tumor suppressor p53 expression, protecting it from MDM2-mediated degradation and inhibiting Sin3A-mediated cell proliferation in compliance with the apoptotic cell density.

Author Biographies

Nezahat Kurt, Department of Medical Biochemistry, Faculty of Medicine, Erzincan Binali Yildirim University, Erzincan, Turkey

Department of Medical Biochemistry, Faculty of Medicine, Erzincan Binali Yildirim University

Nuri Bakan, Department of Medical Biochemistry, Faculty of Medicine, Ataturk University, Erzurum, Turkey

Department of Medical Biochemistry, Faculty of Medicine, Ataturk University, Erzurum, Turkey

Adem Kara, Department of Molecular Biology and Genetics, Faculty of Science, Erzurum Technical University, Erzurum, Turkey

Histology and Embryology, Faculty of Veterinary, Bingol University, Bingol, Turkey

Seçkin Özkanlar, Department of Biochemistry, Faculty of Veterinary, Ataturk University, Erzurum, Turkey

Department of Biochemistry, Faculty of Veterinary, Ataturk University, Erzurum, Turkey

Eda Balkan, Department of Medical Biology, Faculty of Medicine, Ataturk University, Erzurum, Turkey

Department of Medical Biology, Faculty of Medicine, Ataturk University, Erzurum, Turkey

Fatma Betül Özgeriş, Department of Nutrition and Dietetics, Faculty of Healthy Sciences, Ataturk University, Erzurum, Turkey

Department of Nutrition and Dietetics, Faculty of Health Sciences, Ataturk University, Turkey

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2021-12-15

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Kurt, N., Bakan, N., Kara, A., Özkanlar, S., Balkan, E., & Özgeriş, F. B. (2021). Docetaxel Regulates the Interaction of p53 with MDM2 and Sin3A to Suppress MCF-7 Breast Cancer Cells. Natural Products and Biotechnology, 1(2), 64–74. Retrieved from https://natprobiotech.com/index.php/natprobiotech/article/view/16

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Vol. 1 No. 2 (2021)

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