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

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 c...

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Autores principales:	Cing-Yu Chen, Cheng-Hsun Wu, King-Chuen Wu, Lian-Ru Shiao, Chin-Min Chuang, Yuk-Man Leung, Louis W C Chow
Formato:	article
Lenguaje:	EN
Publicado:	Wolters Kluwer Medknow Publications 2021
Materias:	apoptosis breast cancer bt-474 cells ca2+ overload endoplasmic reticulum stress gamma-linolenic acid oxidative stress Physiology QP1-981
Acceso en línea:	https://doaj.org/article/5a55c058ae314ae9ae0727b140c2d0c2
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spelling	oai:doaj.org-article:5a55c058ae314ae9ae0727b140c2d0c22021-11-12T10:09:39ZA basal level of γ-linolenic acid depletes Ca2+ stores and induces endoplasmic reticulum and oxidative stresses to cause death of breast cancer BT-474 cells0304-49202666-005910.4103/cjp.cjp_30_21https://doaj.org/article/5a55c058ae314ae9ae0727b140c2d0c22021-01-01T00:00:00Zhttp://www.cjphysiology.org/article.asp?issn=0304-4920;year=2021;volume=64;issue=4;spage=202;epage=209;aulast=Chenhttps://doaj.org/toc/0304-4920https://doaj.org/toc/2666-0059Gamma-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.Cing-Yu ChenCheng-Hsun WuKing-Chuen WuLian-Ru ShiaoChin-Min ChuangYuk-Man LeungLouis W C ChowWolters Kluwer Medknow Publicationsarticleapoptosisbreast cancerbt-474 cellsca2+ overloadendoplasmic reticulum stressgamma-linolenic acidoxidative stressPhysiologyQP1-981ENChinese Journal of Physiology, Vol 64, Iss 4, Pp 202-209 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	apoptosis breast cancer bt-474 cells ca2+ overload endoplasmic reticulum stress gamma-linolenic acid oxidative stress Physiology QP1-981
spellingShingle	apoptosis breast cancer bt-474 cells ca2+ overload endoplasmic reticulum stress gamma-linolenic acid oxidative stress Physiology QP1-981 Cing-Yu Chen Cheng-Hsun Wu King-Chuen Wu Lian-Ru Shiao Chin-Min Chuang Yuk-Man Leung Louis W C Chow 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
description	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.
format	article
author	Cing-Yu Chen Cheng-Hsun Wu King-Chuen Wu Lian-Ru Shiao Chin-Min Chuang Yuk-Man Leung Louis W C Chow
author_facet	Cing-Yu Chen Cheng-Hsun Wu King-Chuen Wu Lian-Ru Shiao Chin-Min Chuang Yuk-Man Leung Louis W C Chow
author_sort	Cing-Yu Chen
title	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
title_short	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
title_full	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
title_fullStr	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
title_full_unstemmed	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
title_sort	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
publisher	Wolters Kluwer Medknow Publications
publishDate	2021
url	https://doaj.org/article/5a55c058ae314ae9ae0727b140c2d0c2
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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

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