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
| Autor: | Lian-Ru Shiao, Louis W.C. Chow, Cheng-Hsun Wu, Chin-Min Chuang, Yuk-Man Leung, Cing-Yu Chen, King-Chuen Wu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Physiology
Oxidative phosphorylation medicine.disease_cause chemistry.chemical_compound breast cancer gamma-linolenic acid Physiology (medical) medicine oxidative stress QP1-981 cardiovascular diseases gamma-Linolenic acid Ryanodine receptor Endoplasmic reticulum ca2+ overload apoptosis nutritional and metabolic diseases Cell biology chemistry Apoptosis bt-474 cells Unfolded protein response endoplasmic reticulum stress lipids (amino acids peptides and proteins) Cyclopiazonic acid Oxidative stress hormones hormone substitutes and hormone antagonists |
| Zdroj: | Chinese Journal of Physiology, Vol 64, Iss 4, Pp 202-209 (2021) |
| ISSN: | 2666-0059 0304-4920 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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