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Planta Med 2015; 81(10): 838-846
DOI: 10.1055/s-0035-1546132
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Mechanism of Ascorbate-Induced Cell Death in Human Pancreatic Cancer Cells: Role of Bcl-2, Beclin 1 and Autophagy

Masayuki Fukui
1   Department of Pharmacology, Toxicology and Therapeutics, School of Medicine, University of Kansas Medical Center, Kansas City, KS, USA
2   Department of Microbiology, Tropical Biosphere Research Center, University of the Ryukyus, Nishihara, Okinawa, Japan
,
Noriko Yamabe
1   Department of Pharmacology, Toxicology and Therapeutics, School of Medicine, University of Kansas Medical Center, Kansas City, KS, USA
,
Hye-Joung Choi
1   Department of Pharmacology, Toxicology and Therapeutics, School of Medicine, University of Kansas Medical Center, Kansas City, KS, USA
,
Kishore Polireddy
1   Department of Pharmacology, Toxicology and Therapeutics, School of Medicine, University of Kansas Medical Center, Kansas City, KS, USA
,
Qi Chen
1   Department of Pharmacology, Toxicology and Therapeutics, School of Medicine, University of Kansas Medical Center, Kansas City, KS, USA
,
Bao Ting Zhu
1   Department of Pharmacology, Toxicology and Therapeutics, School of Medicine, University of Kansas Medical Center, Kansas City, KS, USA
3   Department of Biology, South University of Science and Technology of China, Shenzhen, Guangdong, China
› Author Affiliations
Further Information

Publication History

received 11 February 2015
revised 18 April 2015

accepted 03 May 2015

Publication Date:
01 July 2015 (online)

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Abstract

The present study investigates the anticancer effect of ascorbate in MIA-PaCa-2 human pancreatic cancer cells using both in vitro and in vivo models, with a focus on assessing the role of oxidative stress and autophagy as important mechanistic elements in its anticancer actions. We showed that ascorbate suppresses the growth of human pancreatic cancer cells via the induction of oxidative stress and caspase-independent cell death. Ascorbate induces the formation of autophagosomes and the presence of autophagy inhibitors suppresses ascorbate-induced cell death. These data suggest that the induction of autophagosome formation contributes to ascorbate-induced pancreatic cancer cell death.

Key words

ascorbate - pancreatic cancer - cell death - autophagy

Supporting Information

 

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