Docosahexaenoic Acid Inhibits Cell Proliferation through a Suppression of c-Myc Protein in Pancreatic Ductal Adenocarcinoma Cells

Treatment of pancreatic cancer by inhibiting the aberrant activation of the survival signaling pathways has received considerable attention. We investigated the probable action of DHA on the suppression of cell proliferation in human pancreatic ductal adenocarcinoma (PDAC) cells. Our results demonst...

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Autores principales:	Jia-Ning Syu, Der-Yen Lee, Hung-Chang Hung, Chia-Ying Li, Hung-Yu Lin, En-Pei Isabel Chiang, Yi-Heng Chen, Shu-Ming Huang, Feng-Yao Tang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	DHA STAT3 CAMKII c-Myc oxidative stress cell apoptosis Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/cf07a4e0e35f4892a9ffdf7f2b386aac
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spelling	oai:doaj.org-article:cf07a4e0e35f4892a9ffdf7f2b386aac2021-11-25T16:27:11ZDocosahexaenoic Acid Inhibits Cell Proliferation through a Suppression of c-Myc Protein in Pancreatic Ductal Adenocarcinoma Cells10.3390/antiox101117212076-3921https://doaj.org/article/cf07a4e0e35f4892a9ffdf7f2b386aac2021-10-01T00:00:00Zhttps://www.mdpi.com/2076-3921/10/11/1721https://doaj.org/toc/2076-3921Treatment of pancreatic cancer by inhibiting the aberrant activation of the survival signaling pathways has received considerable attention. We investigated the probable action of DHA on the suppression of cell proliferation in human pancreatic ductal adenocarcinoma (PDAC) cells. Our results demonstrated that DHA dose-dependently inhibited cell proliferation through an induction of cell cycle arrest in human PDAC cells. DHA suppressed the expression of phosphorylated-Rb (p-Rb), cyclin D1, cyclin E, cyclin A, E2F1 and c-Myc proteins. Blocking the activation of STAT3 signaling pathway led to an inactivation of CAMKII and increased phosphorylation of c-Myc (T58) protein accompanied with decreased expression of c-Myc protein. Treatment of DHA effectively inhibited cell survival through decreased phosphorylation levels of EGFR, STAT3 and CAMKII proteins. The mechanisms of action were associated with increased phosphorylation levels of c-Myc (T58) and instability of c-Myc proteins. DHA inhibited cell survival through an increased GSSG/GSH ratio and oxidative stress level in HPAF-II cells. DHA induced cell apoptosis through increased expression of Bax, c-caspase 3 and c-PARP proteins in HPAF-II cells. Moreover, treatment of DHA significantly inhibited nucleotide synthesis. In conclusion, DHA might significantly suppress the proliferation of PDAC cells and therefore have potential as an anti-cancer therapeutic agent.Jia-Ning SyuDer-Yen LeeHung-Chang HungChia-Ying LiHung-Yu LinEn-Pei Isabel ChiangYi-Heng ChenShu-Ming HuangFeng-Yao TangMDPI AGarticleDHASTAT3CAMKIIc-Mycoxidative stresscell apoptosisTherapeutics. PharmacologyRM1-950ENAntioxidants, Vol 10, Iss 1721, p 1721 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	DHA STAT3 CAMKII c-Myc oxidative stress cell apoptosis Therapeutics. Pharmacology RM1-950
spellingShingle	DHA STAT3 CAMKII c-Myc oxidative stress cell apoptosis Therapeutics. Pharmacology RM1-950 Jia-Ning Syu Der-Yen Lee Hung-Chang Hung Chia-Ying Li Hung-Yu Lin En-Pei Isabel Chiang Yi-Heng Chen Shu-Ming Huang Feng-Yao Tang Docosahexaenoic Acid Inhibits Cell Proliferation through a Suppression of c-Myc Protein in Pancreatic Ductal Adenocarcinoma Cells
description	Treatment of pancreatic cancer by inhibiting the aberrant activation of the survival signaling pathways has received considerable attention. We investigated the probable action of DHA on the suppression of cell proliferation in human pancreatic ductal adenocarcinoma (PDAC) cells. Our results demonstrated that DHA dose-dependently inhibited cell proliferation through an induction of cell cycle arrest in human PDAC cells. DHA suppressed the expression of phosphorylated-Rb (p-Rb), cyclin D1, cyclin E, cyclin A, E2F1 and c-Myc proteins. Blocking the activation of STAT3 signaling pathway led to an inactivation of CAMKII and increased phosphorylation of c-Myc (T58) protein accompanied with decreased expression of c-Myc protein. Treatment of DHA effectively inhibited cell survival through decreased phosphorylation levels of EGFR, STAT3 and CAMKII proteins. The mechanisms of action were associated with increased phosphorylation levels of c-Myc (T58) and instability of c-Myc proteins. DHA inhibited cell survival through an increased GSSG/GSH ratio and oxidative stress level in HPAF-II cells. DHA induced cell apoptosis through increased expression of Bax, c-caspase 3 and c-PARP proteins in HPAF-II cells. Moreover, treatment of DHA significantly inhibited nucleotide synthesis. In conclusion, DHA might significantly suppress the proliferation of PDAC cells and therefore have potential as an anti-cancer therapeutic agent.
format	article
author	Jia-Ning Syu Der-Yen Lee Hung-Chang Hung Chia-Ying Li Hung-Yu Lin En-Pei Isabel Chiang Yi-Heng Chen Shu-Ming Huang Feng-Yao Tang
author_facet	Jia-Ning Syu Der-Yen Lee Hung-Chang Hung Chia-Ying Li Hung-Yu Lin En-Pei Isabel Chiang Yi-Heng Chen Shu-Ming Huang Feng-Yao Tang
author_sort	Jia-Ning Syu
title	Docosahexaenoic Acid Inhibits Cell Proliferation through a Suppression of c-Myc Protein in Pancreatic Ductal Adenocarcinoma Cells
title_short	Docosahexaenoic Acid Inhibits Cell Proliferation through a Suppression of c-Myc Protein in Pancreatic Ductal Adenocarcinoma Cells
title_full	Docosahexaenoic Acid Inhibits Cell Proliferation through a Suppression of c-Myc Protein in Pancreatic Ductal Adenocarcinoma Cells
title_fullStr	Docosahexaenoic Acid Inhibits Cell Proliferation through a Suppression of c-Myc Protein in Pancreatic Ductal Adenocarcinoma Cells
title_full_unstemmed	Docosahexaenoic Acid Inhibits Cell Proliferation through a Suppression of c-Myc Protein in Pancreatic Ductal Adenocarcinoma Cells
title_sort	docosahexaenoic acid inhibits cell proliferation through a suppression of c-myc protein in pancreatic ductal adenocarcinoma cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/cf07a4e0e35f4892a9ffdf7f2b386aac
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Docosahexaenoic Acid Inhibits Cell Proliferation through a Suppression of c-Myc Protein in Pancreatic Ductal Adenocarcinoma Cells

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