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

Masayuki Fukui; Noriko Yamabe; Hye-Joung Choi; Kishore Polireddy; Qi Chen; Bao Ting Zhu

doi:10.1055/s-0035-1546132

Planta Medica, Inhaltsverzeichnis

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

Autor*innen

Masayuki Fukui

¹Department of Pharmacology, Toxicology and Therapeutics, School of Medicine, University of Kansas Medical Center, Kansas City, KS, USA

²Department of Microbiology, Tropical Biosphere Research Center, University of the Ryukyus, Nishihara, Okinawa, Japan
Noriko Yamabe

¹Department of Pharmacology, Toxicology and Therapeutics, School of Medicine, University of Kansas Medical Center, Kansas City, KS, USA
Hye-Joung Choi

¹Department of Pharmacology, Toxicology and Therapeutics, School of Medicine, University of Kansas Medical Center, Kansas City, KS, USA
Kishore Polireddy

¹Department of Pharmacology, Toxicology and Therapeutics, School of Medicine, University of Kansas Medical Center, Kansas City, KS, USA
Qi Chen

¹Department of Pharmacology, Toxicology and Therapeutics, School of Medicine, University of Kansas Medical Center, Kansas City, KS, USA
Bao Ting Zhu

¹Department of Pharmacology, Toxicology and Therapeutics, School of Medicine, University of Kansas Medical Center, Kansas City, KS, USA

³Department of Biology, South University of Science and Technology of China, Shenzhen, Guangdong, China

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

Volltext

Referenzen

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