Endocrine Abstracts (2003) 6 P30

Extracts from the Marine Sponges Anthosigmella varians (AV) and Spongia barbara (SB) Lower Cyclin B1 Levels, Cause a G2/M Cell Cycle Block and Trigger Apoptosis in SW-13 Human Adrenal Carcinoma Cultures

JW Brown1,2, S Cappell1,3, C Perez-Stable1,2 & LM Fishman1,2

1V.A Medical Center, Miami, FL U.S.A.; 2Department of Medicine, University of Miami, Miami, Fl U.S.A.; 3Department of Biology , Marine Science Program, University of Miami, Miami, FL U.S.A.

Many marine sponges have been shown to produce metabolites with cell growth and endocrine altering activities. We tested crude extracts (1.0 mg/ml) from two species (AV and SB) for effects on levels of an important cell cycle regulatory protein, cyclin B1; cell cycle growth-phase (sub-G1/Apoptosis, G1, S, and G2/M), as well as on cell survival in SW-13 human adrenal carcinoma cultures. Polyacrylamide gel electrophoresis studies of cyclin B1 levels indicate a 60-90 % reduction by treatment with the AV or SB extract. EPICS V flow cytometry analysis indicates a 17-fold increase over control cultures in the percentage of these cells entering apoptosis (to 22.6 +/- 1.2 % vs. 1.3 +/- 0.2 % for controls; p<0.010) by AV and an 11-fold increase in this parameter by SB extracts (to 14.4 +/- 4.3 %; p<0.01) after treatment for four days. During this same period, the percentages of cells in G2/M were increased from 11.8 +/- 0.3 % to 18.1 +/- 0.6 % by AV (p<0.01) and to 18.3 +/- 5.4 % by SB (p<0.05). Cell survival studies also indicate an expected time-dependent decline in cell density (i.e.,% confluence) of SW-13 human adrenal carcinoma cultures exposed to either AV or SB relative to control incubations. These experiments indicate that some species of marine sponges have metabolites which are capable of interfering with specific aspects of the cell cycle and, consequently, the proliferation and survival of human adrenal carcinoma cells in culture. This work was supported by the South Florida Veterans Affairs Foundation for Research & Education, the U.S. Department of Veterans Affairs and the Marine Science Honors Program of the University of Miami College of Arts & Sciences.

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