Journal
ONCOTARGETS AND THERAPY
Volume 14, Issue -, Pages 3849-3860Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/OTT.S313933
Keywords
celastrol; natural products; pancreatic cancer; RRM2; DDIT3; MCM4
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Celastrol has been shown to inhibit pancreatic cancer cell growth, induce apoptosis, and inhibit PGE2 production. Its cytotoxic effect is mainly mediated through the modulation of specific genes and signaling pathways.
Background: Pancreatic cancer is one of the most serious and lethal human cancers with a snowballing incidence around the world. The natural product celastrol has also been widely documented as a potent anti-inflammatory, anti-angiogenic, and anti-oxidant. Purpose: To elucidate the antitumor effect of celastrol on pancreatic cancer cells and its modulatory role on whole genome expression. Methods: The antitumor activity of celastrol on a panel of pancreatic cancer cells has been evaluated by Sulforhodamine B assay. Caspase 3/7 and histone-associated DNA fragments assays were done for apoptosis measurement. Additionally, prostaglandin (PGE2) inhibition was evaluated. Moreover, a microarray gene expression profiling was carried out to detect possible key players that modulate the antitumor effects of celastrol on cells of pancreatic cancer. Results: Our findings indicated that celastrol suppresses the cellular growth of pancreatic cancer cells, induces apoptosis, and inhibits PGE2 production. Celastrol modulated many signaling genes and its cytotoxic effect was mainly mediated via over-expression of ATF3 and DDIT3, and down-expression of RRM2 and MCM4. Conclusion: The current study aims to be a starting point to generate a hypothesis on the most significant regulatory genes and for a full dissection of the celastrol possible effects on each single gene to prevent the pancreatic cancer growth.
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