title: Metformin, but not sitagliptin, enhances WP 631-induced apoptotic HepG2 cell death.
abstract: Metformin and sitagliptin are hypoglycemic drugs with potential use in cancer treatment. Evidence indicates that metformin may inhibit the proliferation and growth of various types of cancer cells. Data regarding the relationship between sitagliptin and cancer cells is limited. Therapy based on anthracycline derivatives, mainly doxorubicin, is commonly used in the treatment of resistant liver cancers. WP 631 is a new structural analogue of doxorubicin that exerts an anticancer action by the induction of apoptosis. The aim of this study was to compare the effect of metformin and sitagliptin on WP 631-induced apoptotic cell death in a human hepatocarcinoma cell line (HepG2). HepG2 cancer cells are known to be resistant to chemotherapeutic cytotoxic agents. Both MTT assay and flow cytometry analysis showed that WP 631 reduced the growth of HepG2 cells by apoptosis induction, accompanied by elevated NF-κB and p53 levels. Metformin enhanced the pro-apoptotic effect of WP 631, increasing the NF-κB level but not the p53 level. Sitagliptin did not affect the action of WP 631 in HepG2 cancer cells, however, it increased the p53 level. To conclude, our results suggest that metformin significantly enhances the efficacy of anthracycline derivative, although this effect is not observed in the case of sitagliptin. Therefore, metformin seems to be a good candidate for combined therapy of resistant liver cancer with anthracycline derivatives.
authors.affiliation: Department of Internal Disease, Diabetology and Clinical Pharmacology, Medical University of Lodz, Pomorska 251, 92-213 Lodz, Poland. Electronic address: agnieszka.sliwinska@umed.lodz.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Sliwinska
authors.affiliation: Department of Thermobiology, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.
authors.forename: Aneta
authors.initials: A
authors.lastname: Rogalska
authors.affiliation: Department of Thermobiology, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Marczak
authors.affiliation: Department of Internal Disease, Diabetology and Clinical Pharmacology, Medical University of Lodz, Pomorska 251, 92-213 Lodz, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Kasznicki
authors.affiliation: Department of Internal Disease, Diabetology and Clinical Pharmacology, Medical University of Lodz, Pomorska 251, 92-213 Lodz, Poland.
authors.forename: Jozef
authors.initials: J
authors.lastname: Drzewoski
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D003630:Daunorubicin / Q000031:analogs & derivatives; D056945:Hep G2 Cells; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008687:Metformin / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D000068900:Sitagliptin Phosphate / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D007004:Hypoglycemic Agents; D016328:NF-kappa B; D016159:Tumor Suppressor Protein p53; C104426:WP 631; D008687:Metformin; D000068900:Sitagliptin Phosphate; D003630:Daunorubicin
keywords: Apoptosis; Hepatocarcinoma; Metformin; Sitagliptin; WP 631