Acetogenins from Annonaceae (ACG) are potent inhibitors of the mitochondrial complex I, they present cytotoxic activity on neoplasic lines, including those with multiresistance to drugs. In vivo antitumor activities of some ACG have been reported; however, no information is available regarding the relationship between their cytotoxic activity in cell cultures and their antiproliferative action in vivo. Laherradurin and cherimolin-2 acetogenins were isolated from Annona diversifolia seeds, and their inhibitory potential was analysed in vitro on HeLa and SW-480 cells. Doses containing 1, 10, 100 and 500 times the IC50 obtained from the proliferation assays and multiplied by the weight of the animal, were injected once daily into athymic mice bearing these cancer cell lines; their effect upon tumor growth was measured over a period of 20 days. Laherradurin was more active than cherimolin-2, and it showed in in vitro proliferation assays a similar IC50 in both neoplasic lines. In athymic mice, laherradurin administered in 10x, 100x and 500x doses, reduced the size of HeLa tumors, and with 100x and 500x doses, affected the SW-480 tumor development. These doses were similar to results found with the control drug doxorubicin (p < or = 0.05). On the other hand, cherimolin-2 had an effect on HeLa tumors cells at 100x and 500x doses (p < or = 0.05).
Copyright 2009 John Wiley & Sons, Ltd.