title: Involvement of the Nrf2 pathway in the regulation of pterostilbene-induced apoptosis in HeLa cells via ER stress.
abstract: Among the various cancer cell lines, HeLa cells were found to be sensitive to pterostilbene (Pte), a compound that is enriched in small fruits such as grapes and berries. However, the mechanism involved in the cytotoxicity of Pte has not been fully characterized. Using biochemical and free radical biological experiments in vitro, we identified the pro-apoptotic profiles of Pte and evaluated the level of redox stress-triggered ER stress during HeLa cell apoptosis. The data showed a strong dose-response relationship between Pte exposure and the characteristics of HeLa apoptosis in terms of changes in apoptotic morphology, DNA fragmentation, and activated caspases in the intrinsic apoptotic pathway. During drug exposure, alterations in the intracellular redox homeostasis that favor oxidation were necessary to cause ER stress-related apoptosis, as demonstrated by enzymatic and non-enzymatic redox modulators. A statistically significant and dose-dependent increase (P < 0.05) was found with regard to the unique expression levels of Nrf2/ARE downstream target genes in HeLa cells undergoing late apoptosis, levels that were restored with anti-oxidant application with the Pte treatment. Our research demonstrated that Pte trigged ER stress by redox homeostasis imbalance, which was negatively regulated by a following activation of Nrf2.
authors.affiliation: Key Laboratory of Xinjiang Endemic Phytomedicine Resources, Ministry of Education, Pharmacology Department, School of Pharmacy, Shihezi University, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Xiao-Qin
authors.initials: XQ
authors.lastname: Wang
authors.forename: Han-Yin
authors.initials: HY
authors.lastname: Chen
authors.forename: Bin-Hua
authors.initials: BH
authors.lastname: Liu
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D013267:Stilbenes; C107773:pterostilbene