Expression of heat shock protein 70 modulates the chemoresponsiveness of pancreatic cancer

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10 Citations (Scopus)

Abstract

Background/Aims: Heat shock protein (HSP) 70 is constitutively overexpressed in pancreatic cancer cells (PCCs) and appears to confer protection against chemotherapeutics. We investigated whether modulating HSP 70 increases chemoresponsiveness to gemcitabine in PCCs. Methods: Varying concentrations of quercetin and gemcitabine, either alone or in combination, were added to PCCs (Panc-1 and MiaPaCa- 2). MTT assay was performed to analyze cell viability. HSP 70 expression was assessed by Western blot analysis. Apoptosis was determined by measuring caspase-3 activity. Western blot for the LC3-II protein detected the presence of autophagy. Results: HSP 70 levels were not affected by the incubation of Panc-1 and MiaPaCa-2 cells with gemcitabine, whereas with quercetin, the levels were reduced in both cell lines. The viability of both Panc-1 and MiaPaCa-2 cells significantly decreased with gemcitabine treatment but not with quercetin. A combination of gemcitabine and quercetin decreased the viability of both cell lines in a dose-dependent manner, which was more pronounced than gemcitabine treatment alone. Treatment with either gemcitabine or quercetin augmented caspase-3 activity in both cell lines, and a combination of these compounds further potentiated caspase-3 activity. LC3-II protein expression was negligible with gemcitabine treatment but marked with quercetin. The addition of gemcitabine to quercetin did not potentiate LC3-II protein expression. Conclusions: Modulation of HSP 70 expression with quercetin enhanced the chemoresponsiveness of PCCs to gemcitabine. The mechanism of cell death was both apoptosis and autophagy.

Original languageEnglish
Pages (from-to)739-746
Number of pages8
JournalGut and Liver
Volume7
Issue number6
DOIs
Publication statusPublished - 2013 Nov 1

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gemcitabine
HSP70 Heat-Shock Proteins
Pancreatic Neoplasms
Quercetin
Caspase 3
Autophagy
Cell Line
Western Blotting
Apoptosis
Proteins

Keywords

  • Gemcitabine
  • Heat shock proteins
  • Pancreatic neoplasms
  • Quercetin

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

@article{05e08093a6994dc0acf5d2bad5d80fa6,
title = "Expression of heat shock protein 70 modulates the chemoresponsiveness of pancreatic cancer",
abstract = "Background/Aims: Heat shock protein (HSP) 70 is constitutively overexpressed in pancreatic cancer cells (PCCs) and appears to confer protection against chemotherapeutics. We investigated whether modulating HSP 70 increases chemoresponsiveness to gemcitabine in PCCs. Methods: Varying concentrations of quercetin and gemcitabine, either alone or in combination, were added to PCCs (Panc-1 and MiaPaCa- 2). MTT assay was performed to analyze cell viability. HSP 70 expression was assessed by Western blot analysis. Apoptosis was determined by measuring caspase-3 activity. Western blot for the LC3-II protein detected the presence of autophagy. Results: HSP 70 levels were not affected by the incubation of Panc-1 and MiaPaCa-2 cells with gemcitabine, whereas with quercetin, the levels were reduced in both cell lines. The viability of both Panc-1 and MiaPaCa-2 cells significantly decreased with gemcitabine treatment but not with quercetin. A combination of gemcitabine and quercetin decreased the viability of both cell lines in a dose-dependent manner, which was more pronounced than gemcitabine treatment alone. Treatment with either gemcitabine or quercetin augmented caspase-3 activity in both cell lines, and a combination of these compounds further potentiated caspase-3 activity. LC3-II protein expression was negligible with gemcitabine treatment but marked with quercetin. The addition of gemcitabine to quercetin did not potentiate LC3-II protein expression. Conclusions: Modulation of HSP 70 expression with quercetin enhanced the chemoresponsiveness of PCCs to gemcitabine. The mechanism of cell death was both apoptosis and autophagy.",
keywords = "Gemcitabine, Heat shock proteins, Pancreatic neoplasms, Quercetin",
author = "Hyun, {Jong Jin} and Lee, {Hong Sik} and Bora Keum and Seo, {Yeon Seok} and Jeen, {Yoon Tae} and Hoon-Jai Chun and Soon-Ho Um and Kim, {Chang Duck}",
year = "2013",
month = "11",
day = "1",
doi = "10.5009/gnl.2013.7.6.739",
language = "English",
volume = "7",
pages = "739--746",
journal = "Gut and Liver",
issn = "1976-2283",
publisher = "Joe Bok Chung",
number = "6",

}

TY - JOUR

T1 - Expression of heat shock protein 70 modulates the chemoresponsiveness of pancreatic cancer

AU - Hyun, Jong Jin

AU - Lee, Hong Sik

AU - Keum, Bora

AU - Seo, Yeon Seok

AU - Jeen, Yoon Tae

AU - Chun, Hoon-Jai

AU - Um, Soon-Ho

AU - Kim, Chang Duck

PY - 2013/11/1

Y1 - 2013/11/1

N2 - Background/Aims: Heat shock protein (HSP) 70 is constitutively overexpressed in pancreatic cancer cells (PCCs) and appears to confer protection against chemotherapeutics. We investigated whether modulating HSP 70 increases chemoresponsiveness to gemcitabine in PCCs. Methods: Varying concentrations of quercetin and gemcitabine, either alone or in combination, were added to PCCs (Panc-1 and MiaPaCa- 2). MTT assay was performed to analyze cell viability. HSP 70 expression was assessed by Western blot analysis. Apoptosis was determined by measuring caspase-3 activity. Western blot for the LC3-II protein detected the presence of autophagy. Results: HSP 70 levels were not affected by the incubation of Panc-1 and MiaPaCa-2 cells with gemcitabine, whereas with quercetin, the levels were reduced in both cell lines. The viability of both Panc-1 and MiaPaCa-2 cells significantly decreased with gemcitabine treatment but not with quercetin. A combination of gemcitabine and quercetin decreased the viability of both cell lines in a dose-dependent manner, which was more pronounced than gemcitabine treatment alone. Treatment with either gemcitabine or quercetin augmented caspase-3 activity in both cell lines, and a combination of these compounds further potentiated caspase-3 activity. LC3-II protein expression was negligible with gemcitabine treatment but marked with quercetin. The addition of gemcitabine to quercetin did not potentiate LC3-II protein expression. Conclusions: Modulation of HSP 70 expression with quercetin enhanced the chemoresponsiveness of PCCs to gemcitabine. The mechanism of cell death was both apoptosis and autophagy.

AB - Background/Aims: Heat shock protein (HSP) 70 is constitutively overexpressed in pancreatic cancer cells (PCCs) and appears to confer protection against chemotherapeutics. We investigated whether modulating HSP 70 increases chemoresponsiveness to gemcitabine in PCCs. Methods: Varying concentrations of quercetin and gemcitabine, either alone or in combination, were added to PCCs (Panc-1 and MiaPaCa- 2). MTT assay was performed to analyze cell viability. HSP 70 expression was assessed by Western blot analysis. Apoptosis was determined by measuring caspase-3 activity. Western blot for the LC3-II protein detected the presence of autophagy. Results: HSP 70 levels were not affected by the incubation of Panc-1 and MiaPaCa-2 cells with gemcitabine, whereas with quercetin, the levels were reduced in both cell lines. The viability of both Panc-1 and MiaPaCa-2 cells significantly decreased with gemcitabine treatment but not with quercetin. A combination of gemcitabine and quercetin decreased the viability of both cell lines in a dose-dependent manner, which was more pronounced than gemcitabine treatment alone. Treatment with either gemcitabine or quercetin augmented caspase-3 activity in both cell lines, and a combination of these compounds further potentiated caspase-3 activity. LC3-II protein expression was negligible with gemcitabine treatment but marked with quercetin. The addition of gemcitabine to quercetin did not potentiate LC3-II protein expression. Conclusions: Modulation of HSP 70 expression with quercetin enhanced the chemoresponsiveness of PCCs to gemcitabine. The mechanism of cell death was both apoptosis and autophagy.

KW - Gemcitabine

KW - Heat shock proteins

KW - Pancreatic neoplasms

KW - Quercetin

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U2 - 10.5009/gnl.2013.7.6.739

DO - 10.5009/gnl.2013.7.6.739

M3 - Article

VL - 7

SP - 739

EP - 746

JO - Gut and Liver

JF - Gut and Liver

SN - 1976-2283

IS - 6

ER -