Vol 44: Pristimerin, a quinonemethide triterpenoid, induces apoptosis in pancreatic cancer cells through the inhibition of pro-survival Akt-NF-B-mTOR signaling proteins and anti-apoptotic Bcl-2.Report as inadecuate



 Vol 44: Pristimerin, a quinonemethide triterpenoid, induces apoptosis in pancreatic cancer cells through the inhibition of pro-survival Akt-NF-B-mTOR signaling proteins and anti-apoptotic Bcl-2.


Vol 44: Pristimerin, a quinonemethide triterpenoid, induces apoptosis in pancreatic cancer cells through the inhibition of pro-survival Akt-NF-B-mTOR signaling proteins and anti-apoptotic Bcl-2. - Download this document for free, or read online. Document in PDF available to download.

Download or read this book online for free in PDF: Vol 44: Pristimerin, a quinonemethide triterpenoid, induces apoptosis in pancreatic cancer cells through the inhibition of pro-survival Akt-NF-B-mTOR signaling proteins and anti-apoptotic Bcl-2.
This article is from International Journal of Oncology, volume 44.AbstractLack of effective therapeutics for pancreatic cancer at the present time underscores the dire need for safe and effective agents for the treatment of this malignancy. In the present study, we have evaluated the anticancer activity and the mechanism of action of pristimerin PM, a quinonemethide triterpenoid, against MiaPaCa-2 and Panc-1 pancreatic ductal adenocarcinoma PDA cell lines. Treatment with PM inhibited the proliferation and induced apoptosis in both cell lines as characterized by the increased Annexin V-binding and cleavage of PARP-1 and procaspases -3 -8 and -9. PM also induced mitochondrial depolarization and the release of cytochrome c from the mitochondria. The induction of apoptosis by PM was associated with the inhibition of the pro-survival Akt, NF-κB and mTOR signaling proteins and their downstream intermediaries such as Foxo-3α and cyclin D1 Akt; Cox-2 and VEGF NF-κB; p-S6K1 and p-4E-BP1 mTOR as well as PKCɛ. Treatment with PM also inhibited the expression of anti-apoptotic Bcl-2 and survivin but not Bcl-xL. The downregulation of Bcl-2 by PM was not due to proteasomal or lysosomal proteolytic degradation of Bcl-2, since treatment with PM in the presence of proteasomal inhibitors MG132 or lactacystin LAC or calpain inhibitor MG101 failed to block the downregulation of Bcl-2 by PM. On the other hand, RT-PCR analysis showed the inhibition of Bcl-2 mRNA by PM in a dose-related manner, indicating that inhibition of Bcl-2 by PM is mediated through the suppression of Bcl-2 gene expression. Thus, the mechanistic understanding of the antitumor activity of pristimerin could facilitate in vivo efficacy studies of pristimerin for pancreatic cancer.



Author: DEEB, DORRAH; GAO, XIAOHUA; LIU, YONG BO; PINDOLIA, KIRIT; GAUTAM, SUBHASH C.

Source: https://archive.org/







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