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. 2010 Dec 15;18(1):16-24. doi: 10.1016/j.phymed.2010.06.005. Epub 2010 Jul 16.


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 agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Apoptosis / drug effects*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism*
  • Caspases / metabolism
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cupressaceae / chemistry*
  • DNA Damage / physiology*
  • Female
  • Furans / pharmacology*
  • Furans / therapeutic use
  • Gene Expression / drug effects
  • Humans
  • Lignans / pharmacology*
  • Lignans / therapeutic use
  • Oxidative Stress / drug effects*
  • Phytotherapy
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Plant Stems
  • Poly(ADP-ribose) Polymerases / metabolism
  • Polynucleotide 5'-Hydroxyl-Kinase / metabolism
  • RNA, Small Interfering
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Up-Regulation
  • fas Receptor / metabolism


  • Antineoplastic Agents, Phytogenic
  • FAS protein, human
  • Furans
  • Lignans
  • Plant Extracts
  • RNA, Small Interfering
  • Reactive Oxygen Species
  • Tumor Suppressor Protein p53
  • fas Receptor
  • taiwanin A
  • Poly(ADP-ribose) Polymerases
  • Polynucleotide 5'-Hydroxyl-Kinase
  • Caspases