دورية أكاديمية
Piperlongumine potentiates the effects of gemcitabine in in vitro and in vivo human pancreatic cancer models.
العنوان: | Piperlongumine potentiates the effects of gemcitabine in in vitro and in vivo human pancreatic cancer models. |
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المؤلفون: | Mohammad J; Department of Biological Sciences, North Dakota State University, Fargo, ND 51808, USA., Dhillon H; Department of Biological Sciences, North Dakota State University, Fargo, ND 51808, USA., Chikara S; Department of Biological Sciences, North Dakota State University, Fargo, ND 51808, USA., Mamidi S; Genome Sequencing Center, HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA., Sreedasyam A; Genome Sequencing Center, HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA., Chittem K; Department of Plant Pathology, North Dakota State University, Fargo, ND 51808, USA., Orr M; Department of Statistics, North Dakota State University, Fargo, ND 51808, USA., Wilkinson JC; Department of Chemistry and Biochemistry, North Dakota State University, Fargo, ND 51808, USA., Reindl KM; Department of Biological Sciences, North Dakota State University, Fargo, ND 51808, USA. |
المصدر: | Oncotarget [Oncotarget] 2017 Dec 23; Vol. 9 (12), pp. 10457-10469. Date of Electronic Publication: 2017 Dec 23 (Print Publication: 2018). |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Impact Journals Country of Publication: United States NLM ID: 101532965 Publication Model: eCollection Cited Medium: Internet ISSN: 1949-2553 (Electronic) Linking ISSN: 19492553 NLM ISO Abbreviation: Oncotarget Subsets: PubMed not MEDLINE |
أسماء مطبوعة: | Original Publication: Albany, N.Y. : Impact Journals |
مستخلص: | 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 cells in vitro and in vivo . 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. Competing Interests: CONFLICTS OF INTEREST The authors declair no conflicts of interest. |
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معلومات مُعتمدة: | P20 GM109024 United States GM NIGMS NIH HHS; P30 GM103332 United States GM NIGMS NIH HHS; R15 CA206067 United States CA NCI NIH HHS; U54 GM115458 United States GM NIGMS NIH HHS |
فهرسة مساهمة: | Keywords: RNA-Seq; apoptosis; cell cycle regulation; complementary and alternative therapy; reactive oxygen species |
تواريخ الأحداث: | Date Created: 20180315 Latest Revision: 20220330 |
رمز التحديث: | 20240829 |
مُعرف محوري في PubMed: | PMC5828188 |
DOI: | 10.18632/oncotarget.23623 |
PMID: | 29535819 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1949-2553 |
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DOI: | 10.18632/oncotarget.23623 |