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Autophagy-dependent EIF2AK3 activation compromises ursolic acid-induced apoptosis through upregulation of MCL1 in MCF-7 human breast cancer cells.
Autophagy 2013; 9(2):196-207A

Abstract

Ursolic acid (UA) is a pentacyclic triterpenoid with promising cancer chemopreventive properties. A better understanding of the mechanisms underlying anticancer activity of UA is needed for further development as a clinically useful chemopreventive agent. Here, we found that both endoplasmic reticulum (ER) stress and autophagy were induced by UA in MCF-7 human breast cancer cells. Surprisingly, ER stress was identified as an effect rather than a cause of UA-induced autophagy. Autophagy-dependent ER stress protected the cells from UA-induced apoptosis through EIF2AK3-mediated upregulation of MCL1. Activation of MAPK1/3 but not inhibition of MTOR pathway contributed to UA-induced cytoprotective autophagy in MCF-7 cells. Our findings uncovered a novel cellular mechanism involved in the anticancer activity of UA, and also provided a useful model to study biological significance and mechanisms of autophagy-mediated ER stress.

Authors+Show Affiliations

Department of Nutrition and Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23182854

Citation

Zhao, Chong, et al. "Autophagy-dependent EIF2AK3 Activation Compromises Ursolic Acid-induced Apoptosis Through Upregulation of MCL1 in MCF-7 Human Breast Cancer Cells." Autophagy, vol. 9, no. 2, 2013, pp. 196-207.
Zhao C, Yin S, Dong Y, et al. Autophagy-dependent EIF2AK3 activation compromises ursolic acid-induced apoptosis through upregulation of MCL1 in MCF-7 human breast cancer cells. Autophagy. 2013;9(2):196-207.
Zhao, C., Yin, S., Dong, Y., Guo, X., Fan, L., Ye, M., & Hu, H. (2013). Autophagy-dependent EIF2AK3 activation compromises ursolic acid-induced apoptosis through upregulation of MCL1 in MCF-7 human breast cancer cells. Autophagy, 9(2), pp. 196-207. doi:10.4161/auto.22805.
Zhao C, et al. Autophagy-dependent EIF2AK3 Activation Compromises Ursolic Acid-induced Apoptosis Through Upregulation of MCL1 in MCF-7 Human Breast Cancer Cells. Autophagy. 2013 Feb 1;9(2):196-207. PubMed PMID: 23182854.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Autophagy-dependent EIF2AK3 activation compromises ursolic acid-induced apoptosis through upregulation of MCL1 in MCF-7 human breast cancer cells. AU - Zhao,Chong, AU - Yin,Shutao, AU - Dong,Yinhui, AU - Guo,Xiao, AU - Fan,Lihong, AU - Ye,Min, AU - Hu,Hongbo, Y1 - 2012/11/26/ PY - 2012/11/28/entrez PY - 2012/11/28/pubmed PY - 2013/7/10/medline KW - EIF2AK3 KW - ER stress KW - MCF-7 KW - MCL1 KW - apoptosis KW - autophagy KW - cytoprotection KW - ursolic acid SP - 196 EP - 207 JF - Autophagy JO - Autophagy VL - 9 IS - 2 N2 - Ursolic acid (UA) is a pentacyclic triterpenoid with promising cancer chemopreventive properties. A better understanding of the mechanisms underlying anticancer activity of UA is needed for further development as a clinically useful chemopreventive agent. Here, we found that both endoplasmic reticulum (ER) stress and autophagy were induced by UA in MCF-7 human breast cancer cells. Surprisingly, ER stress was identified as an effect rather than a cause of UA-induced autophagy. Autophagy-dependent ER stress protected the cells from UA-induced apoptosis through EIF2AK3-mediated upregulation of MCL1. Activation of MAPK1/3 but not inhibition of MTOR pathway contributed to UA-induced cytoprotective autophagy in MCF-7 cells. Our findings uncovered a novel cellular mechanism involved in the anticancer activity of UA, and also provided a useful model to study biological significance and mechanisms of autophagy-mediated ER stress. SN - 1554-8635 UR - https://www.unboundmedicine.com/medline/citation/23182854/Autophagy_dependent_EIF2AK3_activation_compromises_ursolic_acid_induced_apoptosis_through_upregulation_of_MCL1_in_MCF_7_human_breast_cancer_cells_ L2 - http://www.tandfonline.com/doi/full/10.4161/auto.22805 DB - PRIME DP - Unbound Medicine ER -