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Article Publish Status: FREE
Abstract Title:

Piperlongumine potentiates the effects of gemcitabine inandhuman pancreatic cancer models.

Abstract Source:

Oncotarget. 2018 Feb 13 ;9(12):10457-10469. Epub 2017 Dec 23. PMID: 29535819

Abstract Author(s):

Jiyan Mohammad, Harsharan Dhillon, Shireen Chikara, Sujan Mamidi, Avinash Sreedasyam, Kishore Chittem, Megan Orr, John C Wilkinson, Katie M Reindl

Article Affiliation:

Jiyan Mohammad

Abstract:

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers due to a late diagnosis and poor response to available treatments. There is a need to identify complementary treatment strategies that will enhance the efficacy and reduce the toxicity of currently used therapeutic approaches. We investigated the ability of a known ROS inducer, piperlongumine (PL), to complement the modest anti-cancer effects of the approved chemotherapeutic agent gemcitabine (GEM) in PDAC cellsand. PDAC cells treated with PL + GEM showed reduced cell viability, clonogenic survival, and growth on Matrigel compared to control and individually-treated cells. Nude mice bearing orthotopically implanted MIA PaCa-2 cells treated with both PL (5 mg/kg) and GEM (25 mg/kg) had significantly lower tumor weight and volume compared to control and single agent-treated mice. RNA sequencing (RNA-Seq) revealed that PL + GEM resulted in significant changes in p53-responsive genes that play a role in cell death, cell cycle, oxidative stress, and DNA repair pathways. Cell culture assays confirmed PL + GEM results in elevated ROS levels, arrests the cell cycle in the G0/G1 phase, and induces PDAC cell death. We propose a mechanism for the complementary anti-tumor effects of PL and GEM in PDAC cells through elevation of ROS and transcription of cell cycle arrest and cell death-associated genes. Collectively, our results suggest that PL has potential to be combined with GEM to more effectively treat PDAC.

Study Type : Animal Study, In Vitro Study

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