Diosgenin potentiates the anticancer effect of doxorubicin and volasertib via regulating polo-like kinase 1 and triggering apoptosis in hepatocellular carcinoma cells.

Autor: Yousef EH; Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt. Ehamdy@horus.edu.eg.; Department of Biochemistry, Faculty of Pharmacy, Horus University-Egypt, Damietta, 34511, Egypt. Ehamdy@horus.edu.eg., El-Mesery ME; Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt., Habeeb MR; Department of Internal Medicine, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt., Eissa LA; Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt. lailaeissa2002@yahoo.com.
Jazyk: angličtina
Zdroj: Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 2024 Jul; Vol. 397 (7), pp. 4883-4894. Date of Electronic Publication: 2024 Jan 02.
DOI: 10.1007/s00210-023-02894-8
Abstrakt: A common approach to cancer therapy is the combination of a natural product with chemotherapy to overcome sustained cell proliferation and chemotherapy resistance obstacles. Diosgenin (DG) is a phytosteroidal saponin that is naturally present in a vast number of plants and has been shown to exert anti-cancer activities against several tumor cells. Herein, we assessed the chemo-modulatory effects of DG on volasertib (Vola) as a polo-like kinase 1 (PLK1) inhibitor and doxorubicin (DOX) in hepatocellular carcinoma (HCC) cell lines. DOX and Vola were applied to two human HCC cell lines (HepG2 and Huh-7) alone or in combination with DG. The cell viability was determined, and gene expressions of PLK1, PCNA, P53, caspase-3, and PARP1 were evaluated by RT-qPCR. Moreover, apoptosis induction was determined by measuring active caspase-3 level using ELISA method. DG enhanced the anticancer effects of Vola and DOX. Moreover, DG enhanced Vola- and DOX-induced cell death by downregulating the expressions of PLK1 and PCNA, elevating the expressions of P53 and active caspase-3. DG showed promising chemo-modulatory effects to Vola and DOX against HCC that may be attributed partly to the downregulation of PLK1 and PCNA, upregulation of tumor suppressor protein P53, and apoptosis induction. Thus, DG combination with chemotherapy may be a promising treatment approach for HCC.
(© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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