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

Antioxidants

Jia-Ning Syu¹  Feng-Yao Tang¹  En-Pei Isabel Chiang²  Hung-Chang Hung³  Shu-Ming Huang⁴  Yi-Heng Chen⁵  Chia-Ying Li⁵  Der-Yen Lee⁶  Hung-Yu Lin⁷ 

[1] Biomedical Science Laboratory, Department of Nutrition, China Medical University, Taichung 40604, Taiwan;Department of Food Science and Biotechnology, National Chung Hsing University, Taichung 402, Taiwan;Department of Internal Medicine, Nantou Hospital, Ministry of Health and Welfare, Nantou City 540, Taiwan;Department of Nutrition, Nantou Hospital, Ministry of Health and Welfare, Nantou City 540, Taiwan;Department of Surgery, Show Chwan Memorial Hospital, Changhua 500, Taiwan;Graduate Institute of Integrated Medicine, China Medical University, Taichung 404333, Taiwan;Research Assistant Center, Show Chwan Memorial Hospital, Changhua 500, Taiwan;

关键词: DHA;    STAT3;    CAMKII;    c-Myc;    oxidative stress;    cell apoptosis;   

DOI  :  10.3390/antiox10111721

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown