Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Clin Cancer Res. 2010 Jan 15;16(2):509-20. doi: 10.1158/1078-0432.CCR-09-1713. Epub 2010 Jan 12.

Mechanisms of ascorbate-induced cytotoxicity in pancreatic cancer.

Author information

  • 1Department of Surgery, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA.

Abstract

PURPOSE:

Pharmacologic concentrations of ascorbate may be effective in cancer therapeutics. We hypothesized that ascorbate concentrations achievable with i.v. dosing would be cytotoxic in pancreatic cancer for which the 5-year survival is <3%.

EXPERIMENTAL DESIGN:

Pancreatic cancer cell lines were treated with ascorbate (0, 5, or 10 mmol/L) for 1 hour, then viability and clonogenic survival were determined. Pancreatic tumor cells were delivered s.c. into the flank region of nude mice and allowed to grow at which time they were randomized to receive either ascorbate (4 g/kg) or osmotically equivalent saline (1 mol/L) i.p. for 2 weeks.

RESULTS:

There was a time- and dose-dependent increase in measured H(2)O(2) production with increased concentrations of ascorbate. Ascorbate decreased viability in all pancreatic cancer cell lines but had no effect on an immortalized pancreatic ductal epithelial cell line. Ascorbate decreased clonogenic survival of the pancreatic cancer cell lines, which was reversed by treatment of cells with scavengers of H(2)O(2). Treatment with ascorbate induced a caspase-independent cell death that was associated with autophagy. In vivo, treatment with ascorbate inhibited tumor growth and prolonged survival.

CONCLUSIONS:

These results show that pharmacologic doses of ascorbate, easily achievable in humans, may have potential for therapy in pancreatic cancer.

PMID:
20068072
[PubMed - indexed for MEDLINE]
PMCID:
PMC2807999
Free PMC Article

Images from this publication.See all images (6)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk