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7,8‐Dihydroxy‐3‐(4‐nitrophenyl)coumarin induces cell death via reactive oxygen species–independent S‐phase cell arrest
Author(s) -
Musa Musiliyu A,
Gbadebo Akintunde J,
Latinwo Lekan M,
Badisa Veera LD
Publication year - 2018
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.22203
Subject(s) - reactive oxygen species , lncap , cytotoxicity , chemistry , programmed cell death , coumarin , viability assay , apoptosis , cell culture , antioxidant , in vitro , cell cycle , cell cycle checkpoint , cell , cytotoxic t cell , biochemistry , cancer cell , biology , cancer , organic chemistry , genetics
We herein report the synthesis and in vitro cytotoxicity of 3‐arylcoumarin derivatives (6a‐f and 7a‐f) in human liver (HepG2), prostate (LNCap), and pancreatic (BxPC3) cancer cell lines. Among the tested compounds, 7,8‐dihydroxy‐3‐(4‐nitrophenyl) coumarin (7b) showed the highest cytotoxicity in the HepG2 cell line. The mechanism of cytotoxic action indicated that compound (7b) arrested HepG2 cells at the S phase of the cell cycle progression, induced loss of mitochondrial membrane potential, and caused reactive oxygen species (ROS)‐independent cell death. The cell viability result of pretreated HepG2 cells with antioxidant N‐acetylcysteine followed by compound (7b) treatment and the free radical scavenging activities of compound (7b) confirmed the ROS‐independent cell death. These results demonstrate that compound (7b) could serve as a valuable template for the development of novel synthetic compounds as potential anticancer agents for hepatocellular carcinoma treatment.