Accession Number:

ADA455889

Title:

2-Methoxyestradiol as a Chemotherapeutic for Prostate Cancer

Descriptive Note:

Annual rept. 1 Apr 2005-31 Mar 2006

Corporate Author:

MIAMI UNIV FL

Personal Author(s):

• Perez-Stable, Carlos

Report Date:

2006-04-01

Pagination or Media Count:

58.0

Abstract:

2-Methoxyestradiol 2-ME is an endogenous metabolite of estradiol with promise for cancer chemotherapy, including advanced prostate cancer. Our hypothesis is one of the cancer-specific mechanisms whereby 2-ME exerts its anti-prostate cancer activity is the deregulated activation of cyclin B1cdk1 kinase during the cell cycle, which results in the induction of apoptotic cell death. Several experimental results support this hypothesis 1 there is a positive correlation between the levels of cyclin B1 protein and the ability of 2-ME to increase G2M cell cycle arrest and apoptosis in prostate cancer cells 2 inhibition of cdk1 activity lowers 2-ME-mediated apoptosis while overexpression of cyclin B1 increases 2-ME-mediated apoptosis 3 low doses of 2-ME and docetaxel can increase G2M cell cycle arrest and apoptosis in prostate cancer cell lines and in the G T transgenic mouse model of prostate cancer greater than either drug alone. We conclude that 2-ME can increase apoptosis in prostate cancer cells because of the expression of cyclin B1 protein, which is minimally expressed in normal cells.

Descriptors:

• *CHEMOTHERAPY
• *PROSTATE CANCER
• *TRANSCRIPTION(GENETICS)
• *APOPTOSIS
• CYCLES
• CORRELATION
• HYPOTHESES
• MICE
• DEATH
• CELLS(BIOLOGY)

Subject Categories:

• Biochemistry
• Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE