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

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_name

Cancer Lett

journal_title

Cancer letters

authors

Kumar S,Inigo JR,Kumar R,Chaudhary AK,O'Malley J,Balachandar S,Wang J,Attwood K,Yadav N,Hochwald S,Wang X,Chandra D

doi

10.1016/j.canlet.2017.10.029

subject

Has Abstract

pub_date

2018-01-28 00:00:00

pages

82-93

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(17)30666-3

journal_volume

413

pub_type

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