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Parthenolide suppresses pancreatic cell growth by autophagy-mediated apoptosis

Authors Liu W, Wang X, Sun J, Yang Y, Li W, Song J

Received 14 July 2016

Accepted for publication 17 September 2016

Published 23 January 2017 Volume 2017:10 Pages 453—461

DOI https://doi.org/10.2147/OTT.S117250

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 2

Editor who approved publication: Dr Samir Farghaly

Weifeng Liu,1 Xinshuai Wang,2 Junjun Sun,1 Yanhui Yang,1 Wensheng Li,1 Junxin Song1

1Department of Hepatobiliary Surgery, 2Department of Oncology, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luo Yang, China


Abstract: Pancreatic cancer is an aggressive malignancy and is unresponsive to conventional chemotherapies. Parthenolide, a sesquiterpene lactone isolated from feverfew, has exhibited potent anticancer effects against various cancers. The purpose of this report was to investigate the effect and underlying mechanism of parthenolide in human pancreatic cancer Panc-1 and BxPC3 cells. The results demonstrated that parthenolide suppressed the growth and induced apoptosis of Panc-1 and BxPC3 pancreatic cancer cells with the half maximal inhibitory concentration (IC50) ranging between 7 and 9 µM after 24 h of treatment. Significant autophagy was induced by parthenolide treatment in pancreatic cancer cells. Parthenolide treatment concentration-dependently increased the percentage of autophagic cells and significantly increased the expression levels of p62/SQSTM1, Beclin 1, and LC3II in Panc-1 cells. Punctate LC3II staining confirmed autophagy. Furthermore, inhibiting autophagy by chloroquine, 3-methyladenine, or LC3II siRNA significantly blocked parthenolide-induced apoptosis, suggesting that parthenolide induced apoptosis through autophagy in this study. In conclusion, these studies established that parthenolide inhibits pancreatic cell growth by autophagy-mediated apoptosis. Data of the present study suggest that parthenolide can serve as a potential chemotherapeutic agent for pancreatic cancer.

Keywords:
parthenolide, pancreatic cancer, autophagy, apoptosis, P62, cleaved PAPRP

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