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ORIGINAL ARTICLE
Year : 2021  |  Volume : 64  |  Issue : 4  |  Page : 202-209

A basal level of γ-linolenic acid depletes Ca2+ stores and induces endoplasmic reticulum and oxidative stresses to cause death of breast cancer BT-474 cells


1 Department of Physiology, China Medical University, Taichung, Taiwan
2 Department of Anatomy, China Medical University, Taichung, Taiwan
3 Department of Anesthesiology, Chang Gung Memorial Hospital; Chang Gung University of Science and Technology, Chiayi, Taiwan
4 Department of Emergency Medicine, China Medical University Hospital, Taichung, Taiwan
5 State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Taipa, Macau; UNIMED Medical Institute; Organisation for Oncology and Translational Research, Hong Kong, China

Correspondence Address:
Prof. Yuk-Man Leung
Department of Physiology, China Medical University, Taichung
Taiwan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/cjp.cjp_30_21

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Gamma-linolenic acid (GLA), a natural fatty acid obtained from oils of various vegetables and seeds, has been demonstrated as an anticancer agent. In this work, we investigated the anticancer effects of GLA on breast cancer BT-474 cells. GLA at 30 μM, a concentration reportedly within the range of circulating concentrations in clinical studies, caused apoptotic cell death. GLA caused an elevation in mitochondrial Ca2+ level and a decrease in mitochondrial membrane potential. GLA treatment depleted cyclopiazonic acid (CPA)-sensitive Ca2+ store and triggered substantial Ca2+ influx. Intracellular Ca2+ release triggered by GLA was suppressed by 3 μM xestospongin C (XeC, IP3 receptor-channel blocker) and 100 μM ryanodine (ryanodine receptor-channel blocker), suggesting that the Ca2+ release was via IP3 receptor-channel and ryanodine receptor-channel. Increased expressions of p-eIF2α and CHOP were observed in GLA-treated cells, suggesting GLA-treated cells had increased expressions of p-eIF2α and CHOP, which suggest endoplasmic reticulum (ER) stress. In addition, GLA elicited increased production of reactive oxygen species. Taken together, our results suggest a basal level of GLA induced apoptotic cell death by causing Ca2+ overload, mitochondrial dysfunction, Ca2+ store depletion, ER stress, and oxidative stress. This is the first report to show that GLA caused Ca2+ store depletion and ER stress. GLA-induced Ca2+ store depletion resulted from opening of IP3 receptor-channel and ryanodine receptor-channel.


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