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.