Received for publication February 5, 2007.
Revised April 24, 2007.
Accepted for publication April 26, 2007.

A Cannabinoid Anticancer Quinone, HU-331, is More Potent and Less Cardiotoxic than Doxorubicin - a Comparative In-Vivo Study

Abstract

Several quinones have been found to be effective in the treatment of some forms of cancer, however their cumulative heart toxicity limits their use. The cannabinoid quinone HU-331 is highly effective against tumor xenografts in nude mice. We report now a comparison of the anticancer activity of HU-331 and its cardiotoxicity with those of doxorubicin in-vivo. General toxicity was assayed in Sabra, nude and SCID-NOD mice. The anti-cancer activity in-vivo was assessed by measurement of the tumors with an external caliper in HT-29 and Raji tumor-bearing mice and by weighing the excised tumors. Left ventricular function was evaluated with transthoracic echocardiography. Myelotoxicity was evaluated by blood cell count. Cardiac troponin T (cTnT) plasma levels were determined by immunoassay. HU-331 was found to be much less cardiotoxic than doxorubicin. The control and the HU-331-treated groups gained weight, while the doxorubicin-treated group lost weight during the study. In HT-29 colon carcinoma, the tumor weight in the HU-331-treated group was 54% smaller than in the control group and 30% smaller than in the doxorubicin-treated group. In Raji lymphoma, the tumor weight in the HU-331-treated group was 65% smaller than in the control group and 33% smaller than in the doxorubicin-treated group. In contrast to doxorubicin, HU-331 did not generate reactive oxygen species (ROS) in mice hearts (measured by protein carbonylation levels and malondialdehyde levels). In-vivo HU-331 was more active and less toxic than doxorubicin and thus it has a high potential for development as a new anticancer drug.

Key words: cancer, cannabinoid, cardiotoxicity, chemotherapy, doxorubicin, quinone