Sanguinarine causes DNA damage and p53-independent cell death in human colon cancer cell lines

The benzophenanthridine alkaloid sanguinarine has antimicrobial and possibly anticancer properties but it is not clear to what extent these activities involve DNA damage. Thus, we studied its ability to cause DNA single and double strand breaks, as well as increased levels of 8-oxodeoxyguanosine, in...

Full description

Saved in:
Bibliographic Details
Published in:Chemico-biological interactions 2008-03, Vol.172 (1), p.63-71
Main Authors: Matkar, Smita S., Wrischnik, Lisa A., Hellmann-Blumberg, Utha
Format: Article
Language:English
Subjects:
8-Oxodeoxyguanosine
Alkaloids - chemistry
Alkaloids - pharmacology
Antineoplastic Agents, Phytogenic - chemistry
Antineoplastic Agents, Phytogenic - pharmacology
Apoptosis
Apoptosis - drug effects
Benzophenanthridines - chemistry
Benzophenanthridines - pharmacology
Cell Line, Tumor
Colonic Neoplasms - drug therapy
Colonic Neoplasms - genetics
Colonic Neoplasms - pathology
DNA Damage - drug effects
DNA strand breaks
Humans
Isoquinolines - chemistry
Isoquinolines - pharmacology
Molecular Structure
Oxidation-Reduction
Oxidative DNA damage
p53
Sanguinarine
Time Factors
Tumor Suppressor Protein p53 - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The benzophenanthridine alkaloid sanguinarine has antimicrobial and possibly anticancer properties but it is not clear to what extent these activities involve DNA damage. Thus, we studied its ability to cause DNA single and double strand breaks, as well as increased levels of 8-oxodeoxyguanosine, in human colon cancer cells and found DNA damage consistent with oxidation. Since the tumor suppressor p53 is frequently involved in inducing apoptosis following DNA damage we investigated the effect of sanguinarine in wild type, p53-mutant and p53-null colon cancer cell lines. We found them to be equally sensitive to this plant compound, indicating that cell death is not mediated by p53 in this case. In addition, our observation that apoptosis induced by sanguinarine is initiated very rapidly raised the question whether there is enough time for cellular signaling in response to DNA damage. Moreover, the abundance of double strand breaks is not consistent with only oxidative damage to DNA. We conclude that the majority of DNA double strand breaks in sanguinarine-treated cells are likely the result, rather than the cause, of apoptotic cell death and that apoptosis induced by sanguinarine is independent of p53 and most likely independent of DNA damage.
ISSN:0009-2797
1872-7786
DOI:10.1016/j.cbi.2007.12.006