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

Phytomedicine : International Journal of Phytotherapy and Phytopharmacology
Lie-Fen ShyurSheng-Yang Wang

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, p21(Cip1), and p27(Kip1) and down-regulate the G(2)/M checkpoint cyclin-dependent kinase1 (Cdk1)-cyclin A/B, leading to induction of G(2)/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...Continue Reading

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Citations

Nov 21, 2015·Journal of Receptor and Signal Transduction Research·Ramar Vanajothi, Pappu Srinivasan
Jun 20, 2015·Archivum Immunologiae Et Therapiae Experimentalis·Ammad Ahmad FarooqiHsueh-Wei Chang
Jun 3, 2015·Journal of Biomaterials Science. Polymer Edition·Onon BatnyamSatoshi Fujita
Oct 21, 2017·International Journal of Molecular Sciences·Artur BeberokEwa Buszman
Sep 28, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Paramita Basu, Camelia Maier
Jun 7, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Somchai SriwiriyajanPotchanapond Graidist

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