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

Planta Med. 2015 Jul;81(10):838-46. doi: 10.1055/s-0035-1546132. Epub 2015 Jul 1.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism*
  • Ascorbic Acid / pharmacology*
  • Autophagy / drug effects*
  • Beclin-1
  • Cell Death / drug effects
  • Cell Line, Tumor / drug effects
  • Female
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice, Nude
  • Microtubule-Associated Proteins / metabolism
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • RNA, Small Interfering
  • Reactive Oxygen Species / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • BECN1 protein, human
  • Beclin-1
  • MAP1LC3B protein, human
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Small Interfering
  • Reactive Oxygen Species
  • Ascorbic Acid