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- Title
Physapruin A Exerts Endoplasmic Reticulum Stress to Trigger Breast Cancer Cell Apoptosis via Oxidative Stress.
- Authors
Yu, Tzu-Jung; Shiau, Jun-Ping; Tang, Jen-Yang; Farooqi, Ammad Ahmad; Cheng, Yuan-Bin; Hou, Ming-Feng; Yen, Chia-Hung; Chang, Hsueh-Wei
- Abstract
Physalis plants are commonly used traditional medicinal herbs, and most of their extracts containing withanolides show anticancer effects. Physapruin A (PHA), a withanolide isolated from P. peruviana, shows antiproliferative effects on breast cancer cells involving oxidative stress, apoptosis, and autophagy. However, the other oxidative stress-associated response, such as endoplasmic reticulum (ER) stress, and its participation in regulating apoptosis in PHA-treated breast cancer cells remain unclear. This study aims to explore the function of oxidative stress and ER stress in modulating the proliferation and apoptosis of breast cancer cells treated with PHA. PHA induced a more significant ER expansion and aggresome formation of breast cancer cells (MCF7 and MDA-MB-231). The mRNA and protein levels of ER stress-responsive genes (IRE1α and BIP) were upregulated by PHA in breast cancer cells. The co-treatment of PHA with the ER stress-inducer (thapsigargin, TG), i.e., TG/PHA, demonstrated synergistic antiproliferation, reactive oxygen species generation, subG1 accumulation, and apoptosis (annexin V and caspases 3/8 activation) as examined by ATP assay, flow cytometry, and western blotting. These ER stress responses, their associated antiproliferation, and apoptosis changes were partly alleviated by the N-acetylcysteine, an oxidative stress inhibitor. Taken together, PHA exhibits ER stress-inducing function to promote antiproliferation and apoptosis of breast cancer cells involving oxidative stress.
- Subjects
CANCER cells; ENDOPLASMIC reticulum; OXIDATIVE stress; BREAST cancer; BREAST; REACTIVE oxygen species
- Publication
International Journal of Molecular Sciences, 2023, Vol 24, Issue 10, p8853
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms24108853