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- Title
The Roles of 4β-Hydroxywithanolide E from Physalis peruviana on the Nrf2-Anti-Oxidant System and the Cell Cycle in Breast Cancer Cells.
- Authors
Peng, Chieh Yu; You, Bang Jau; Lee, Chia Lin; Wu, Yang Chang; Lin, Wen Hsin; Lu, Te Ling; Chang, Fei-Ching; Lee, Hong Zin
- Abstract
4-Hydroxywithanolide E is an active component of the extract of Physalis peruviana that has been reported to exhibit antitumor effects. Although the involvement of reactive oxygen species (ROS) production and the ataxia-telangiectasia mutated protein (ATM)-dependent DNA damage signaling pathway in 4-hydroxywithanolide E-induced apoptosis of breast cancer MCF-7 cells was demonstrated in our previous study, the relationship between ROS production and the cellular defense system response in 4-hydroxywithanolide E-induced cell death requires further verification. The present study suggests that ROS play an important role in 4-hydroxywithanolide E-induced MCF-7 cell death in which anti-oxidants, such as glutathione or N-acetylcysteine, can resist the 4-hydroxywithanolide E-induced accumulation of ROS and cell death. Furthermore, N-acetylcysteine or glutathione can reverse the 4-hydroxywithanolide E-induced changes in the cell cycle distribution and the expression of cell cycle regulators. We found that the 4-hydroxywithanolide E-induced ROS accumulation was correlated with the upregulation of Nrf2 and Nrf2-downstream genes, such as antioxidative defense enzymes. In general, the activity of Nrf2 is regulated by the Ras signalling pathway. However, we demonstrated that Nrf2 was activated during 4-hydroxywithanolide E-induced MCF-7 cell death in spite of the 4-hydroxywithanolide E-induced inhibition of the Ras/Raf/ERK pathway. The activity and protein expression of superoxide dismutase and catalase were involved in the 4-hydroxywithanolide E-induced ROS production in MCF-7 cells. Furthermore, 4-hydroxywithanolide E was demonstrated to significantly reduce the sizes of the tumor nodules in the human breast cancer MDA-MB231 xenograft tumor model.
- Subjects
TAIWAN; BREAST tumor prevention; GENES; ENZYME metabolism; REACTIVE oxygen species; ALTERNATIVE medicine; ANIMAL experimentation; ANTINEOPLASTIC agents; ANTIOXIDANTS; APOPTOSIS; BIOLOGICAL assay; BIOLOGICAL models; CELL cycle; CELL death; CELLULAR signal transduction; GLUTATHIONE; MEDICINAL plants; MICE; PHOSPHOTRANSFERASES; PROBABILITY theory; RESEARCH funding; SUPEROXIDE dismutase; T-test (Statistics); WESTERN immunoblotting; XENOGRAFTS; PLANT extracts; STATISTICAL significance; ACETYLCYSTEINE; DESCRIPTIVE statistics; IN vitro studies; IN vivo studies; PHARMACODYNAMICS
- Publication
American Journal of Chinese Medicine, 2016, Vol 44, Issue 3, p617
- ISSN
0192-415X
- Publication type
Article
- DOI
10.1142/S0192415X16500348