This abstract may be posted elsewhere but I couldn't find it.
I'm guessing this is related to the ASCO presentation in May. It's scheduled for 8am tomorrow morning.
[PROC. AMER. ASSOC. CANCER RES. 40, March 1999]
Copyright © 1999 by the American Association for Cancer Research
#3224 Induction of apoptosis in prostate tumor cells by hydroxymethylacylfulvene (HMAF) and oxaliplatin (Ox-Pt).Woynarowska, B.A., Higdon, A.L., Munoz, R.M. and Woynarowski, J.M. The University of Texas Health Science Center, San Antonio, TX 78248 and Cancer Therapy and Research Center, San Antonio, TX 78245.
Targeting apoptosis is particularly relevant to prostate cancer since it is a disease of impeded cell death rather than of accelerated growth. This investigation evaluated pro-apoptotic properties of two novel clinical antitumor drugs, hydroxymethylfulvene (HMAF) and oxaliplatin. HMAF growth inhibitory activity (GI50 of 0.03 - 0.35 µM) against 6 human prostate cell lines correlated with drug uptake. Oxaliplatin was less potent than HMAF (GI50 of 0.2 - 5 µM). Time and concentration-dependent induction and progression of apoptosis by HMAF and Ox-Pt was observed in all tumor prostate cell lines. The level of induced apoptosis as measured by DNA fragmentation and multivariate flow cytometry, depended on cell line and decreased with androgen dependency of cells. Apoptosis by HMAF was accompanied by reactive oxygen species (ROS) generation and a modest release of cytochrome C (~2 fold increase over control after 4 h with 25 µM HMAF). Ox-Pt did not cause cytochrome C leakage to the cytoplasm. HMAF induced apoptosis was not preceded by caspase-3 activation and was not affected by caspase-3 inhibitors. It was abrogated, however, by a broad-spectrum caspase inhibitor Z-VAD-fmk. The results suggest the potential of HMAF and Ox-Pt as apoptosis targeting agents in prostate cancers.
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Schedule: 4/13/1999 8:00 a.m. |
