CELL-GROWTH INHIBITORY EFFECTS OF CAULERPENYNE, A SESQUITERPENOID FROM THE MARINE-ALGAE CAULERPA-TAXIFOLIA

Caulerpa taxifolia (Vahl) C. Agardh (Ulvophyceae, Caulerpales) is an a lgae of tropical origin that was accidentally introduced into the Medi terranean in 1984. Caulerpenyne (Cau) is the major metabolite present in Caulerpa taxifolia. This metabolite has previously been shown to be cytotoxic against cell lines in culture as in KB cells and fibroblast s from hamsters. Cau along with 6 other drugs representative of the ma jor classes of anticancer products was tested against 8 cancer cell li nes of human origin. Cau demonstrated growth-inhibitory effects in all cases with some variability between cell lines; this inter-cell varia bility was, however, less marked than that observed with the anticance r drug tested. Cells of colorectal cancer origin were the most sensiti ve to the presence of Cau with IC50 values of 6.1 and 7.7 mu M. Increa sing the duration of contact between Cau and the cells from 75 min to 29.5 hr did not improve the cytotoxic efficacy of this compound. When Cau was pre-incubated in the culture medium for from 7 to 83 min befor e being exposed to CAL 27 cells (head and neck cancer origin), there w as a constant loss of cytostatic action of Cau as a function of Cau pr e-incubation time. As the bovine serum albumin concentration increased in the culture medium, the concentration-response curves showed a con stant shift towards the right, indicating a loss of cytostatic activit y of Cau. In the presence of Cau, cells in culture clearly exhibited a n early and marked shift into S phase followed by a blockade into the premitotic G2 M phase. Possible targets for CAU remain to be identifie d. Cau needs to be tested on tumor bearing animals to confirm this pro mising antiproliferative activity.