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Transcriptome Analysis of Piperlongumine-Treated Human Pancreatic Cancer Cells Reveals Involvement of Oxidative Stress and Endoplasmic Reticulum Stress Pathways

Journal of Medicinal Food 2016년 19권 6호 p.578 ~ 585
Dhillon Harsharan, Mamidi Sujan, McClean Phillip, Reindl Katie M.,
소속 상세정보
 ( Dhillon Harsharan ) - North Dakota State University Department of Biological Sciences
 ( Mamidi Sujan ) - North Dakota State University Department of Plant Sciences
 ( McClean Phillip ) - North Dakota State University Department of Plant Sciences
 ( Reindl Katie M. ) - North Dakota State University Department of Biological Sciences

Abstract


Piperlongumine (PL), an alkaloid obtained from long peppers, displays antitumorigenic properties for a variety of human cell- and animal-based models. The aim of this study was to identify the underlying molecular mechanisms for PL anticancer effects on human pancreatic cancer cells. RNA sequencing (RNA-seq) was used to identify the effects of PL on the transcriptome of MIA PaCa-2 human pancreatic cancer cells. PL treatment of pancreatic cancer cells resulted in differential expression of 683 mRNA transcripts with known protein functions, 351 of which were upregulated and 332 of which were downregulated compared to control-treated cells. Transcripts associated with oxidative stress, endoplasmic reticulum (ER) stress, and unfolded protein response pathways were significantly overexpressed with PL treatment. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to validate the RNA-seq results, which included upregulation of HO-1, IRE1α, cytochrome c, and ASNS. The results provide key insight into the mechanisms by which PL alters cancer cell physiology and identify that activation of oxidative stress and ER stress pathways is a critical avenue for PL anticancer effects.

키워드

ER stress; oxidative stress; pancreatic cancer; piperlongumine; RNA sequencing; transcriptomics

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