Effects of Epothilone A in Combination with the Antidiabetic Drugs Metformin and Sitagliptin in HepG2 Human Hepatocellular Cancer Cells: Role of Transcriptional Factors NF-κB and p53

Rogalska, Aneta; Sliwinska, Agnieszka; Kasznicki, Jacek; Drzewoski, Jozef; Marczak, Agnieszka

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자료유형: 학술저널

저자정보: Rogalska, Aneta (Department of Medical Biophysics, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz) Sliwinska, Agnieszka (Department of Internal Medicine, Diabetology and Clinical Pharmacology, Medical University of Lodz) Kasznicki, Jacek (Department of Internal Medicine, Diabetology and Clinical Pharmacology, Medical University of Lodz) Drzewoski, Jozef (Department of Internal Medicine, Diabetology and Clinical Pharmacology, Medical University of Lodz) Marczak, Agnieszka (Department of Medical Biophysics, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz)

저널정보: 아시아태평양암예방학회 Asian Pacific journal of cancer prevention : APJCP Asian Pacific journal of cancer prevention : APJCP 제17권 제3호

발행연도: 2016.1

수록면: 993 - 1,001 (9page)

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Type 2 diabetes mellitus patients are at increased risk of many forms of malignancies, especially of the pancreas, colon and hepatocellular cancer. Unfortunately, little is known of the possible interaction between antidiabetic drugs and anticancer agents. The present study investigates the influence of metformin (MET) and sitagliptin (SITA) on the in vitro anticancer activity of the microtubule depolymerization inhibitor agent epothilone A (EpoA). Hepatocellular liver carcinoma cell line (HepG2) viability and apoptosis were determined by the MTT test and by double staining with PO-PRO-1 and 7-aminoactinomycin D, respectively, after treatment with EpoA, metformin or sitagliptin. The levels of nuclear factor NF-${\kappa}B$ and p53 were evaluated in the presence and absence of inhibitors. While EpoA and MET inhibited HepG2 cell proliferation, SITA did not. EpoA and SITA induced higher p53 levels than MET. All tested drugs increased the level of NF-${\kappa}B$. Only MET enhanced the proapoptotic effect of EpoA. The EpoA+MET combination evoked the highest cytotoxic effect on HepG2 cells and led to apoptosis independent of p53, decreasing the level of NF-${\kappa}B$. These findings support the link between NF-${\kappa}B$ and p53 in the modulation of apoptotic effects in HepG2 cells treated by EpoA. Our studies indicate that the combination of EpoA and MET applied in subtoxic doses has a stronger cytotoxic effect on liver cancer cells than each of the compounds alone. The therapeutic advantages of the combination of EpoA with MET may be valuable in the treatment of patients with diabetes mellitus type 2 (T2DM) and liver cancer.

#Apoptosis #epothilone A #hepatocarcinoma #metformin #sitagliptin

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Rogalska, Aneta

소속기관 Department of Medical Biophysics, Institute of Biophysics, Faculty of Biology and Environmental Prot