Publications
Detailed Information
Mitomycin C and doxorubicin elicit conflicting signals by causing accumulation of cyclin E prior to p21(WAF1/CIP1) elevation in human hepatocellular carcinoma cells
Cited 4 time in
Web of Science
Cited 5 time in Scopus
- Authors
- Issue Date
- 2012-01
- Publisher
- Demetrios A. Spandidos Ed. & Pub.
- Citation
- International Journal of Oncology, Vol.40 No.1, pp.277-286
- Abstract
- Proteins involved in the G, phase of the cell cycle are aberrantly expressed, sometimes in mutated forms, in human cancers including human hepatocellular carcinoma. Upon attack by a DNA-damaging anticancer drug, a cell arrests at the G, phase; this is a safety feature prohibiting entry of DNA-damaged cells into S-phase. p21(WAF1/CIP1) prevents damaged cells from progressing to the next cell cycle. Here, we show that, in response to mitomycin C and doxorubicin, human hepatocellular carcinoma cells generate conflicting signals, mediated by cycl in E and p21(WAF1/CIP1), which respectively accelerates and represses cell cycle transition. Exposure to these anticancer drugs led to rapid accumulation of cyclin E in both p53-proficient HepG2 and p53-deficient Hep3B cells. Such anticancer drug-induced cyclin E accumulation influenced the G(1)-S-phase transition, but not DNA fragmentation-mediated death. In p53-proficient HepG2 cells, accumulation of cyclin E was followed by an increase in the level of p53-dependent p21(WAF1/CIP1), thereby inhibiting further the G(1)-S-phase transition. Sublethal drug concentrations also induced rapid accumulation of cyclin E. but p21(WAF1/CIP1) accumulation was delayed, further facilitating the CO-phase transition. Eventually, most cells arrested in G(2)/M. Thus, mitomycin C- or doxorubicin-induced conflicting signals, mediated by cyclin E and p21(WAF1/CIP1), are in play in human hepatocellular carcinoma cells. Damaged G, cells either immediately enter S-phase, or do not do so at all, depending on the extent of DNA damage.
- ISSN
- 1019-6439
- Files in This Item:
- There are no files associated with this item.
- Appears in Collections:
Item View & Download Count
Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.