Docosahexaenoic Acid Inhibits Cell Proliferation through a Suppression of c-Myc Protein in Pancreatic Ductal Adenocarcinoma Cells
| Autor: | Shu-Ming Huang, Yi-Heng Chen, Chia-Ying Li, Hung-Chang Hung, Der-Yen Lee, En-Pei Isabel Chiang, Jia-Ning Syu, Feng-Yao Tang, Hung-Yu Lin |
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| Rok vydání: | 2021 |
| Předmět: |
CAMKII
Cell cycle checkpoint Cyclin E Physiology Clinical Biochemistry Cyclin A pancreatic ductal adenocarcinoma RM1-950 nucleotide synthesis Biochemistry Article STAT3 Cyclin D1 Ca2+/calmodulin-dependent protein kinase oxidative stress Molecular Biology biology cell apoptosis Chemistry Cell growth Cell Biology DHA c-Myc Apoptosis biology.protein Cancer research Phosphorylation Therapeutics. Pharmacology |
| Zdroj: | Antioxidants Antioxidants, vol 10, iss 11 Volume 10 Issue 11 Antioxidants, Vol 10, Iss 1721, p 1721 (2021) |
| ISSN: | 2076-3921 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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