Activation of autophagy and PPAR gamma protect colon cancer cells against apoptosis induced by interactive effects of butyrate and DHA in a cell type-dependent manner: The role of cell differentiation

0471936 - BFÚ 2017 RIV US eng J - Článek v odborném periodiku
Tylichová, Zuzana - Straková, Nicol - Vondráček, Jan - Vaculová, Alena - Kozubík, Alois - Hofmanová, Jiřina
Activation of autophagy and PPAR gamma protect colon cancer cells against apoptosis induced by interactive effects of butyrate and DHA in a cell type-dependent manner: The role of cell differentiation.
Journal of Nutritional Biochemistry. Roč. 39, JAN2017 (2017), s. 145-155. ISSN 0955-2863. E-ISSN 1873-4847
Grant CEP: GA ČR GA13-09766S
Institucionální podpora: RVO:68081707
Klíčová slova: polyunsaturated fatty-acids * histone deacetylase inhibitors * docosahexaenoic acid
Kód oboru RIV: BO - Biofyzika
Impakt faktor: 4.414, rok: 2017

The short-chain and n-3 polyunsaturated fatty acids exhibit anticancer properties, and they may mutually interact within the colon. However, the molecular mechanisms of their action in colon cancer cells are still not fully understood. Our study focused on the mechanisms responsible for the diverse effects of sodium butyrate (NaBt), in particular when interacting with docosahexaenoic acid (DHA), in distinct colon cancer cell types, in which NaBt either induces cell differentiation or activates programmed cell death involving mitochondrial pathway. NaBt activated aufophagy both in HT-29 cells, which are sensitive to induction of differentiation, and in nondifferentiating HCT-116 cells. However, autophagy supported cell survival only in HT-29 cells. Combination of NaBt with DHA-promoted cell death, especially in HCT-116 cells and after longer time intervals. The inhibition of autophagy both attenuated differentiation and enhanced apoptosis in HT-29 cells treated with NaBt and DHA, but it had no effect in HCT-116 cells. NaBt, especially in combination with DHA, activated PPAR gamma in both cell types. PPAR gamma silencing decreased differentiation and increased apoptosis only in HT-29 cells, therefore we verified the role of caspases in apoptosis, differentiation and also PPAR gamma activity using a pan-caspase inhibitor. In summary, our data suggest that diverse responses of colon cancer cells to fatty acids may rely on their sensitivity to differentiation, which may in turn depend on distinct engagement of autophagy, caspases and PPAR gamma. These results contribute to understanding of mechanisms underlying differential effects of NaBt, when interacting with other dietary fatty acids, in colon cancer cells. (C) 2016 Elsevier Inc. All rights reserved.
Trvalý link: http://hdl.handle.net/11104/0269298