Taiwanin A inhibits MCF-7 cancer cell activity through induction of oxidative stress, upregulation of DNA damage checkpoint kinases, and activation of p53 and FasL/Fas signaling pathways
Resource
Phytomedicine
Journal
Phytomedicine
Pages
16-24
Date Issued
2010
Date
2010
Author(s)
Abstract
This study investigates the anti-MCF-7 breast cancer cell effects and the underlying pharmacological activity and mechanism of taiwanin A, a major lignan isolated from Taiwania cryptomerioides. Our results show that taiwanin A time-dependently induced reactive oxygen species level and DNA damage in MCF-7 cells, which were likely activated kinases ataxia telangiectasia mutated (ATM) and checkpoint kinase (Chk). Taiwanin A could also up-regulate p53, phosphorylated p53, p21Cip1, and p27Kip1 and down-regulate the G2/M checkpoint cyclin-dependent kinase1 (Cdk1)-cyclin A/B, leading to induction of G2/M cell-cycle arrest in MCF-7 cells. Blockade of p53 gene expression by siRNA further demonstrated that the cell-cycle arrest induced by taiwanin A was p53-dependent. The FasL/Fas-mediated apoptotic signaling cascade was involved in taiwanin A-induced apoptosis via activation of caspases-10 and -7 (but not caspase-8), and proteolytic cleavage of poly(ADP-ribose) polymerase (PARP). In contrast, mitochondria-initiated apoptotic pathway was not involved. This is the first report to delineate novel mechanism of the action of taiwanin A against MCF-7 cells, suggesting this lignan may have value for development as an anti-breast cancer agent. ? 2010 Elsevier GmbH.
Subjects
Breast cancer; DNA damage checkpoint kinases; FasL/Fas signaling pathway; Oxidative stress; Taiwania cryptomerioides; Taiwanin A
SDGs
Other Subjects
ATM protein; caspase 10; caspase 7; caspase 8; checkpoint kinase; cyclin A; cyclin B; cyclin dependent kinase 1; cyclin dependent kinase inhibitor 1; cyclin dependent kinase inhibitor 1B; Fas antigen; Fas ligand; lignan; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase; protein p53; protein serine threonine kinase; reactive oxygen metabolite; small interfering RNA; taiwanin a; unclassified drug; antineoplastic activity; apoptosis; article; breast cancer; cancer cell culture; cell cycle arrest; cell cycle G2 phase; cell cycle M phase; controlled study; DNA damage; down regulation; drug inhibition; drug isolation; drug mechanism; gene expression; gene mutation; human; human cell; medicinal plant; mitochondrion; oxidative stress; priority journal; protein degradation; protein phosphorylation; signal transduction; taiwania cryptomerioides; upregulation; Antigens, CD95; Antineoplastic Agents, Phytogenic; Apoptosis; Breast Neoplasms; Caspases; Cell Cycle; Cell Line, Tumor; Cupressaceae; DNA Damage; Female; Furans; Gene Expression; Humans; Lignans; Oxidative Stress; Phytotherapy; Plant Extracts; Plant Stems; Poly(ADP-ribose) Polymerases; Polynucleotide 5'-Hydroxyl-Kinase; Reactive Oxygen Species; RNA, Small Interfering; Signal Transduction; Tumor Suppressor Protein p53; Up-Regulation; Ataxia telangiectasia; Taiwania cryptomerioides
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