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 Lettjournal_title
Cancer lettersauthors
Kumar S,Inigo JR,Kumar R,Chaudhary AK,O'Malley J,Balachandar S,Wang J,Attwood K,Yadav N,Hochwald S,Wang X,Chandra Ddoi
10.1016/j.canlet.2017.10.029subject
Has Abstractpub_date
2018-01-28 00:00:00pages
82-93eissn
0304-3835issn
1872-7980pii
S0304-3835(17)30666-3journal_volume
413pub_type
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