Transcriptome analysis of piperlongumine-treated human pancreatic cancer cells reveals involvement of oxidative stress and endoplasmic reticulum stress pathways

Harsharan Dhillon, Sujan Mamidi, Phillip Mcclean, Katie M. Reindl

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)578-585
Number of pages8
JournalJournal of Medicinal Food
Volume19
Issue number6
DOIs
StatePublished - Jun 1 2016

Fingerprint

Endoplasmic Reticulum Stress
Gene Expression Profiling
Pancreatic Neoplasms
Oxidative Stress
RNA Sequence Analysis
Cytochromes c1
Piper
Unfolded Protein Response
Cell Physiological Phenomena
Heat-Shock Proteins
piperlonguminine
Transcriptome
Alkaloids
Reverse Transcription
Up-Regulation
Down-Regulation
Animal Models
Western Blotting
Polymerase Chain Reaction
Messenger RNA

Keywords

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

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Transcriptome analysis of piperlongumine-treated human pancreatic cancer cells reveals involvement of oxidative stress and endoplasmic reticulum stress pathways. / Dhillon, Harsharan; Mamidi, Sujan; Mcclean, Phillip; Reindl, Katie M.

In: Journal of Medicinal Food, Vol. 19, No. 6, 01.06.2016, p. 578-585.

Research output: Contribution to journalArticle

@article{dacebd6e2bc949cfbc9d5e96af95df3b,
title = "Transcriptome analysis of piperlongumine-treated human pancreatic cancer cells reveals involvement of oxidative stress and endoplasmic reticulum stress pathways",
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.",
keywords = "ER stress, RNA sequencing, oxidative stress, pancreatic cancer, piperlongumine, transcriptomics",
author = "Harsharan Dhillon and Sujan Mamidi and Phillip Mcclean and Reindl, {Katie M.}",
year = "2016",
month = "6",
day = "1",
doi = "10.1089/jmf.2015.0152",
language = "English (US)",
volume = "19",
pages = "578--585",
journal = "Journal of Medicinal Food",
issn = "1096-620X",
publisher = "Mary Ann Liebert Inc.",
number = "6",

}

TY - JOUR

T1 - Transcriptome analysis of piperlongumine-treated human pancreatic cancer cells reveals involvement of oxidative stress and endoplasmic reticulum stress pathways

AU - Dhillon, Harsharan

AU - Mamidi, Sujan

AU - Mcclean, Phillip

AU - Reindl, Katie M.

PY - 2016/6/1

Y1 - 2016/6/1

N2 - 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.

AB - 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.

KW - ER stress

KW - RNA sequencing

KW - oxidative stress

KW - pancreatic cancer

KW - piperlongumine

KW - transcriptomics

UR - http://www.scopus.com/inward/record.url?scp=84974555985&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84974555985&partnerID=8YFLogxK

U2 - 10.1089/jmf.2015.0152

DO - 10.1089/jmf.2015.0152

M3 - Article

C2 - 27119744

AN - SCOPUS:84974555985

VL - 19

SP - 578

EP - 585

JO - Journal of Medicinal Food

JF - Journal of Medicinal Food

SN - 1096-620X

IS - 6

ER -