These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Time-dependent changes in factors involved in the apoptotic process in human ovarian cancer cells as a response to cisplatin.
    Author: Kolfschoten GM, Hulscher TM, Schrier SM, van Houten VM, Pinedo HM, Boven E.
    Journal: Gynecol Oncol; 2002 Mar; 84(3):404-12. PubMed ID: 11855878.
    Abstract:
    OBJECTIVES: Apoptosis is believed to be a major mechanism of cisplatin-induced cell death. We investigated the kinetics of apoptosis in four human ovarian cancer cell lines treated with cisplatin to obtain insight into the role and the behavior of a variety of factors involved in this process. METHODS: The cell lines A2780, H134, and IGROV-1 (all wild-type p53) and OVCAR-3 (mutant p53) were exposed to cisplatin for 1 h and the antiproliferative effects were measured after 96 h. At various time points up to 96 h after the 1-h exposure to the individual 90% growth-inhibiting cisplatin concentrations, FACS analysis and May-Grünwald Giemsa staining were carried out to determine the extent of apoptosis. At the same time points protein expression levels of p53, p21/WAF1, Bax, and Bcl-2 and the activity of caspase-3 were measured. FACS analysis was also carried out to determine changes in cell cycle distribution as a response to cisplatin. RESULTS: The four cell lines differed in sensitivity to cisplatin. A2780 was the most sensitive and IGROV-1 was the least sensitive. In contrast, IGROV-1 cells showed the highest percentage of apoptosis (30-40%), while A2780 had the lowest percentage (6-14%) (r = 0.99). The occurrence of apoptosis was not dependent on functional p53. Of interest, caspase-3 activity was in line with the percentage of apoptosis and preceded DNA fragmentation and the visualization of condensed nuclei. Wild-type p53 cells accumulated in the S phase, while OVCAR-3 arrested in the G2/M phase. The protein expression levels of p53, p21/WAF1, Bax, and Bcl-2 varied in time, but were not related to the apoptotic behavior of the cells. Upregulation of p53 was already evident before activation of caspase-3. CONCLUSIONS: Time-dependent changes in the various factors involved in the apoptotic process induced by equitoxic doses of cisplatin vary strongly among the cell lines. Caspase-3 activation plays an important role in cisplatin-induced apoptosis and this precedes morphological changes. The ability of cells to enter apoptosis, however, does not seem to predict sensitivity to cisplatin.
    [Abstract] [Full Text] [Related] [New Search]