Antimitotic and cytotoxic activity of climacostol on tumoral mammalian cells.

The freshwater ciliate Climacostomum virens defends itself against predators by discharging the toxin climacostol (1,3-dihydroxy-5-[(Z)-20-nonenyl]benzene), a resorcinolic lipid contained in its extrusomes (Miyake et al. 2003, Eur. J. Protistol. 39: 25–36). Like other natural chemically related compounds, exerts a dose-dependent cytotoxic effect on tumoral mammalian cell lines (Buonanno et al. 2005, J. Eukaryot. Microbiol. 52:38S). Based on this evidence, we have now examined the effects of chemically synthesized climacostol (Masaki et al. 2004, Tetrahedron 60: 7041–7048) on the proliferation of human promyelocytic leukaemia cells (HL60 line), and squamous carcinoma cells (A431 line) plus, as control, of non-tumoral cells derived from mice Leydig cells (TM3 line). It was observed that: (i) climacostol inhibits the growth of all cell lines used in dose-dependent manner, but the HL60 and A431 cells are significantly more sensitive to the toxin than TM3 cells; (ii) the cytotoxicity of climacostol (used at a concentration of 10 mg/ml, 24 h of incubation, and detected by the LDH-cytotoxicity test) is appreciably stronger on the tumoral cell lines (60% and 41% cytotoxic activity for the A431 and HL60 cells, respectively) than on the TM3 cells (23% cytotoxic activity). It was in addition observed (by using a fluorescent dye technique) that climacostol induces apoptosis, rather than necrosis, in all the cell lines used. These results indicate that climacostol possesses interesting antitumoral biological activities and encourage further in vivo investigations to assess its potential use in cancer chemotherapy.