Nimbolide reduces CD44 positive cell population and induces mitochondrial apoptosis in pancreatic cancer cells

Nimbolide reduces CD44 positive cell population and induces mitochondrial apoptosis in pancreatic... Pancreatic ductal adenocarcinoma (PDAC) is highly aggressive disease and current treatment regimens fail to effectively cure PDAC. Development of resistance to current therapy is one of the key reasons for this outcome. Nimbolide (NL), a triterpenoid obtained from Azadirachta indica, exhibits anticancer properties in various cancer including PDAC cells. However, the underlying mechanism of this anticancer agent in PDAC cells remains undefined. We show that NL exerts a higher level of apoptotic cell death compared to the first-line agent gemcitabine for PDAC, as well as other anticancer agents including sorafenib and curcumin. The anticancer efficacy of NL was further evidenced by a reduction in the CD44+ as well as cancer stem-like cell (CSC) population, as it causes decreased sphere formation. Mechanistically, the anticancer efficacy of NL associates with reduced mutant p53 as well as increased mitochondrial activity in the form of increased mitochondrial reactive oxygen species and mitochondrial mass. Together, this study highlights the therapeutic potential of NL in mutant p53 expressing pancreatic cancer. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Cancer Letters Elsevier

Nimbolide reduces CD44 positive cell population and induces mitochondrial apoptosis in pancreatic cancer cells

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Publisher
Elsevier
Copyright
Copyright © 2017 Elsevier B.V.
ISSN
0304-3835
D.O.I.
10.1016/j.canlet.2017.10.029
Publisher site
See Article on Publisher Site

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is highly aggressive disease and current treatment regimens fail to effectively cure PDAC. Development of resistance to current therapy is one of the key reasons for this outcome. Nimbolide (NL), a triterpenoid obtained from Azadirachta indica, exhibits anticancer properties in various cancer including PDAC cells. However, the underlying mechanism of this anticancer agent in PDAC cells remains undefined. We show that NL exerts a higher level of apoptotic cell death compared to the first-line agent gemcitabine for PDAC, as well as other anticancer agents including sorafenib and curcumin. The anticancer efficacy of NL was further evidenced by a reduction in the CD44+ as well as cancer stem-like cell (CSC) population, as it causes decreased sphere formation. Mechanistically, the anticancer efficacy of NL associates with reduced mutant p53 as well as increased mitochondrial activity in the form of increased mitochondrial reactive oxygen species and mitochondrial mass. Together, this study highlights the therapeutic potential of NL in mutant p53 expressing pancreatic cancer.

Journal

Cancer LettersElsevier

Published: Jan 28, 2018

References

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