Oxidative-Stress-Mediated ER Stress Is Involved in Regulating Manoalide-Induced Antiproliferation in Oral Cancer Cells.

Abstract

Manoalide provides preferential antiproliferation of oral cancer but is non-cytotoxic to normal cells by modulating reactive oxygen species (ROS) and apoptosis. Although ROS interplays with endoplasmic reticulum (ER) stress and apoptosis, the influence of ER stress on manoalide-triggered apoptosis has not been reported. The role of ER stress in manoalide-induced preferential antiproliferation and apoptosis was assessed in this study. Manoalide induces a higher ER expansion and aggresome accumulation of oral cancer than normal cells. Generally, manoalide differentially influences higher mRNA and protein expressions of ER-stress-associated genes (PERK, IRE1α, ATF6, and BIP) in oral cancer cells than in normal cells. Subsequently, the contribution of ER stress on manoalide-treated oral cancer cells was further examined. ER stress inducer, thapsigargin, enhances the manoalide-induced antiproliferation, caspase 3/7 activation, and autophagy of oral cancer cells rather than normal cells. Moreover, N-acetylcysteine, an ROS inhibitor, reverses the responses of ER stress, aggresome formation, and the antiproliferation of oral cancer cells. Consequently, the preferential ER stress of manoalide-treated oral cancer cells is crucial for its antiproliferative effect.

• Authors: Sheng-Yao Peng, Jen-Yang Tang, Ting-Hsun Lan, Jun-Ping Shiau, Kuan-Liang Chen, Jiiang-Huei Jeng, Ching-Yu Yen, Hsueh-Wei Chang
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 24 Issue 4 (Feb 16 2023) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 36835397 (Publication Type: Journal Article)

Chemical References

• Endoribonucleases
• manoalide
• Protein Serine-Threonine Kinases
• Reactive Oxygen Species

Topics

• Humans
• Apoptosis
• Cell Line, Tumor
• Endoplasmic Reticulum Stress
• Endoribonucleases (metabolism)
• Mouth Neoplasms (metabolism, pathology)
• Oxidative Stress
• Protein Serine-Threonine Kinases (metabolism)
• Reactive Oxygen Species (metabolism)