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Cytotoxic effects of the Annonaceous acetogenin, bullatacin, were studied in multidrug-resistant (MDR) human mammary adenocarcinoma (MCF-7/Adr) cells vs. the parental non-resistant wild type (MCF-7/wt) cells. Bullatacin was effectively cytotoxic to the MCF-7/Adr cells while it was more cytostatic to the MCF-7/wt cells. ATP depletion is the mode of action of the Annonaceous acetogenins, and these agents offer a special advantage in the chemotherapeutic treatment of MDR tumors that have ATP-dependent mechanisms.