title: Gliclazide may have an antiapoptotic effect related to its antioxidant properties in human normal and cancer cells.
abstract: Experimental and clinical studies suggest that gliclazide may protect pancreatic β-cells from apoptosis induced by an oxidative stress. However, the precise mechanism(s) of this action are not fully understood and requires further clarification. Therefore, using human normal and cancer cells we examined whether the anti-apoptotic effects of this sulfonylurea is due to its free radical scavenger properties. Hydrogen peroxide (H(2)O(2)) as a model trigger of oxidative stress was used to induce cell death. Our experiments were performed on human normal cell line (human umbilical vein endothelial cell line, HUVEC-c) and human cancer cell lines (human mammary gland cell line, Hs578T; human pancreatic duct epithelioid carcinoma cell line, PANC-1). To assess the effect of gliclazide the cells were pre-treated with the drug. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay was employed to measure the impact of gliclazide on cell viability. Generation of reactive oxygen species, mitochondrial membrane potential (∆Ψ(m)), and intracellular Ca(2+) concentration [Ca(2+)] were monitored. Furthermore, the morphological changes associated with apoptosis were determined using double staining with Hoechst 33258-propidium iodide (PI). Gliclazide protects the tested cells from H(2)O(2)-induced cell death most likely throughout the inhibition of ROS production. Moreover, the drug restored loss of ΔΨ(m) and diminished intracellular [Ca(2+)] evoked by H(2)O(2). Double staining with Hoechst 33258-PI revealed that pre-treatment with gliclazide diminished the number of apoptotic cells. Our findings indicate that gliclazide may protect both normal and cancer human cells against apoptosis induced by H(2)O(2). It appears that the anti-apoptotic effect of the drug is most likely associated with reduction of oxidative stress.
authors.affiliation: Department of Internal Medicine, Diabetology and Clinical Pharmacology, Medical University of Lodz, Parzeczewska 35, Zgierz, 95-100, Lodz, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Sliwinska
authors.forename: Aneta
authors.initials: A
authors.lastname: Rogalska
authors.forename: Marzena
authors.initials: M
authors.lastname: Szwed
authors.forename: Jacek
authors.initials: J
authors.lastname: Kasznicki
authors.forename: Zofia
authors.initials: Z
authors.lastname: Jozwiak
authors.forename: Jozef
authors.initials: J
authors.lastname: Drzewoski
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005907:Gliclazide / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D007477:Ions; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008856:Microscopy, Fluorescence
chemical_list: D000975:Antioxidants; D007477:Ions; D006861:Hydrogen Peroxide; D005907:Gliclazide; D002118:Calcium