Open AccessInduction of apoptosis by pinostrobin in human cervical cancer cells: Possible mechanism of action
Author(s) -
Alka Jaudan,
Sapna Sharma,
Sri Nurestri Abd Malek,
Aparna Dixit
Publication year - 2018
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0191523
Subject(s) - apoptosis , hela , fadd , cytochrome c , mitochondrion , microbiology and biotechnology , biology , cancer cell , caspase , intrinsic apoptosis , dna damage , caspase 8 , reactive oxygen species , signal transduction , chemistry , programmed cell death , cell , biochemistry , cancer , dna , genetics
Pinostrobin (P N ) is a naturally occurring dietary bioflavonoid, found in various medicinal herbs/plants. Though anti-cancer potential of many such similar constituents has been demonstrated, critical biochemical targets and exact mechanism for their apoptosis-inducing actions have not been fully elucidated. The present study was aimed to investigate if P N induced apoptosis in cervical cancer cells (HeLa) of human origin. It is demonstrated that P N at increasing dose effectivity reduced the cell viability as well as GSH and NO 2 - levels. Condensed nuclei with fragmented chromatin and changes in mitochondrial matrix morphology clearly indicated the role of mitochondria in P N induced apoptosis. A marked reduction in mitochondrial membrane potential and increased ROS production after P N treatment showed involvement of free radicals, which in turn further augment ROS levels. P N treatment resulted in DNA damage, which could have been triggered by an increase in ROS levels. Decrease in apoptotic cells in the presence of caspase 3 inhibitor in P N -treated cells suggested that P N induced apoptosis via caspase dependent pathways. Additionally, a significant increase in the expression of proteins of extrinsic (TRAIL R1/DR4, TRAIL R2/DR5, TNF RI/TNFRSF1A, FADD, Fas/TNFRSF6) and intrinsic pathway (Bad, Bax, HTRA2/Omi, SMAC/Diablo, cytochrome C, Pro-Caspase-3, Cleaved Caspase-3) was observed in the cells exposed to P N . Taken together, these observations suggest that P N efficiently induces apoptosis through ROS mediated extrinsic and intrinsic dependent signaling pathways, as well as ROS mediated mitochondrial damage in HeLa cells.