Autophagy in pancreatic cancer: An emerging mechanism of cell death

Nameeta Mujumdar, Ashok Saluja

Research output: Contribution to journalShort survey

37 Citations (Scopus)

Abstract

Pancreatic cancer, the fourth leading cause of cancer-related death in the United States, is resistant to current chemotherapies. Therefore, identification of different pathways of cell death is important to develop novel therapeutics. Our previous study has shown that triptolide, a diterpene triepoxide, inhibits the growth of pancreatic cancer cells in vitro and prevents tumor growth in vivo. However, the mechanism by which triptolide kills pancreatic cancer cells was not known, hence, this study aimed at elucidating it. Our study reveals that triptolide kills diverse types of pancreatic cancer cells by two different pathways; it induces caspase-dependent apoptotic death in some cell lines and death via a caspase-independent autophagic pathway in the other cell lines tested. Triptolide-induced autophagy requires autophagy-specific genes, atg5 or beclin 1 and its inhibition results in cell death via the apoptotic pathway, whereas inhibition of both autophagy and apoptosis rescues triptolide-mediated cell death. Our study shows for the first time that induction of autophagy by triptolide has a pro-death role in pancreatic cancer cells. Since triptolide kills diverse pancreatic cancer cells by different mechanisms, it makes an attractive chemotherapeutic agent for future use against a broad spectrum of pancreatic cancers.

Original languageEnglish (US)
Pages (from-to)997-998
Number of pages2
JournalAutophagy
Volume6
Issue number7
DOIs
StatePublished - Oct 1 2010
Externally publishedYes

Fingerprint

Autophagy
Pancreatic Neoplasms
Cell Death
Caspases
Cell Line
Diterpenes
Growth
triptolide
Neoplasms
Apoptosis
Drug Therapy
Genes

Keywords

  • Apoptosis
  • Caspase-3
  • Pancreatic cancer
  • Triptolide

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Autophagy in pancreatic cancer : An emerging mechanism of cell death. / Mujumdar, Nameeta; Saluja, Ashok.

In: Autophagy, Vol. 6, No. 7, 01.10.2010, p. 997-998.

Research output: Contribution to journalShort survey

Mujumdar, Nameeta ; Saluja, Ashok. / Autophagy in pancreatic cancer : An emerging mechanism of cell death. In: Autophagy. 2010 ; Vol. 6, No. 7. pp. 997-998.
@article{3aa8f4c0c33047ca81fba95c5f6bfc43,
title = "Autophagy in pancreatic cancer: An emerging mechanism of cell death",
abstract = "Pancreatic cancer, the fourth leading cause of cancer-related death in the United States, is resistant to current chemotherapies. Therefore, identification of different pathways of cell death is important to develop novel therapeutics. Our previous study has shown that triptolide, a diterpene triepoxide, inhibits the growth of pancreatic cancer cells in vitro and prevents tumor growth in vivo. However, the mechanism by which triptolide kills pancreatic cancer cells was not known, hence, this study aimed at elucidating it. Our study reveals that triptolide kills diverse types of pancreatic cancer cells by two different pathways; it induces caspase-dependent apoptotic death in some cell lines and death via a caspase-independent autophagic pathway in the other cell lines tested. Triptolide-induced autophagy requires autophagy-specific genes, atg5 or beclin 1 and its inhibition results in cell death via the apoptotic pathway, whereas inhibition of both autophagy and apoptosis rescues triptolide-mediated cell death. Our study shows for the first time that induction of autophagy by triptolide has a pro-death role in pancreatic cancer cells. Since triptolide kills diverse pancreatic cancer cells by different mechanisms, it makes an attractive chemotherapeutic agent for future use against a broad spectrum of pancreatic cancers.",
keywords = "Apoptosis, Caspase-3, Pancreatic cancer, Triptolide",
author = "Nameeta Mujumdar and Ashok Saluja",
year = "2010",
month = "10",
day = "1",
doi = "10.4161/auto.6.7.13334",
language = "English (US)",
volume = "6",
pages = "997--998",
journal = "Autophagy",
issn = "1554-8627",
publisher = "Landes Bioscience",
number = "7",

}

TY - JOUR

T1 - Autophagy in pancreatic cancer

T2 - An emerging mechanism of cell death

AU - Mujumdar, Nameeta

AU - Saluja, Ashok

PY - 2010/10/1

Y1 - 2010/10/1

N2 - Pancreatic cancer, the fourth leading cause of cancer-related death in the United States, is resistant to current chemotherapies. Therefore, identification of different pathways of cell death is important to develop novel therapeutics. Our previous study has shown that triptolide, a diterpene triepoxide, inhibits the growth of pancreatic cancer cells in vitro and prevents tumor growth in vivo. However, the mechanism by which triptolide kills pancreatic cancer cells was not known, hence, this study aimed at elucidating it. Our study reveals that triptolide kills diverse types of pancreatic cancer cells by two different pathways; it induces caspase-dependent apoptotic death in some cell lines and death via a caspase-independent autophagic pathway in the other cell lines tested. Triptolide-induced autophagy requires autophagy-specific genes, atg5 or beclin 1 and its inhibition results in cell death via the apoptotic pathway, whereas inhibition of both autophagy and apoptosis rescues triptolide-mediated cell death. Our study shows for the first time that induction of autophagy by triptolide has a pro-death role in pancreatic cancer cells. Since triptolide kills diverse pancreatic cancer cells by different mechanisms, it makes an attractive chemotherapeutic agent for future use against a broad spectrum of pancreatic cancers.

AB - Pancreatic cancer, the fourth leading cause of cancer-related death in the United States, is resistant to current chemotherapies. Therefore, identification of different pathways of cell death is important to develop novel therapeutics. Our previous study has shown that triptolide, a diterpene triepoxide, inhibits the growth of pancreatic cancer cells in vitro and prevents tumor growth in vivo. However, the mechanism by which triptolide kills pancreatic cancer cells was not known, hence, this study aimed at elucidating it. Our study reveals that triptolide kills diverse types of pancreatic cancer cells by two different pathways; it induces caspase-dependent apoptotic death in some cell lines and death via a caspase-independent autophagic pathway in the other cell lines tested. Triptolide-induced autophagy requires autophagy-specific genes, atg5 or beclin 1 and its inhibition results in cell death via the apoptotic pathway, whereas inhibition of both autophagy and apoptosis rescues triptolide-mediated cell death. Our study shows for the first time that induction of autophagy by triptolide has a pro-death role in pancreatic cancer cells. Since triptolide kills diverse pancreatic cancer cells by different mechanisms, it makes an attractive chemotherapeutic agent for future use against a broad spectrum of pancreatic cancers.

KW - Apoptosis

KW - Caspase-3

KW - Pancreatic cancer

KW - Triptolide

UR - http://www.scopus.com/inward/record.url?scp=77957663027&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77957663027&partnerID=8YFLogxK

U2 - 10.4161/auto.6.7.13334

DO - 10.4161/auto.6.7.13334

M3 - Short survey

C2 - 20818166

AN - SCOPUS:77957663027

VL - 6

SP - 997

EP - 998

JO - Autophagy

JF - Autophagy

SN - 1554-8627

IS - 7

ER -