Cytotoxicity, oxidative stress, and apoptosis in K562 leukemia cells induced by an active compound from pyrano-pyridine derivatives. (October 2018)

• Record Type: Journal Article
• Authors: Mahdavi, M; Asghari, S; Rahnamay, M; Dehghan, G; Feizi, MAH; Balalaie, S
• Is Part Of: Human & experimental toxicology. Volume 37:Number 10(2018)
• Page Start: 1105
• Page End: 1116
• Publication Date: 2018-10
• Subjects: Apoptosis -- pyrano-pyridine -- oxidative stress -- 4-CP.P -- K562 cells; Toxicology -- Periodicals; 615.9
• DOI: 10.1177/0960327118756719
• Languages: English
• ISSNs: 0960-3271

Abstract

Recent studies have reported the potential of pyrano-pyridine compounds in inhibiting cell growth and apoptosis induction in cancer cells. Here, we investigated the effect of new pyrano-pyridine derivatives on proliferation, oxidative damages, and apoptosis in K562 leukemia cells. Among different tested compounds, we found 8-(4-chlorobenzylidene)-2-amino-4-(4-chlorophenyl)-5, 6, 7, 8-tetrahydro-6-phenethyl-4H-pyrano-[3, 2-c]pyridine-3-carbonitrile (4-CP.P) as the most effective compound with IC50 value of 20 μM. Gel electrophoresis, fluorescence microscopy, and flow cytometry analyses indicated the apoptosis induction ability of 4-CP.P in K562 cells. Further analyses revealed that 4-CP.P induces significant increase in cellular reactive oxygen species production, lipid peroxidation, protein oxidation, and total thiol depletion. Interestingly, while 4-CP.P significantly increased the activity of superoxide dismutase, it reduced the catalase activity in a time-dependent manner. These data propose that 4-CP.P treatment causes free radicals accumulation that ultimately leads to oxidative stress condition and apoptosis induction. Therefore, we report the 4-CP.P as a novel, potent compound as a chemotherapeutic agent in cancer treatment.