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 [3S,4R-p-benzoquinone-3-hydroxy-2-p-mentha-(1,8)-dien-3-yl-5-pentyl] 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 anticancer 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, whereas 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 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.

• Authors: Natalya M Kogan, Michael Schlesinger, Maximilian Peters, Gergana Marincheva, Ronen Beeri, Raphael Mechoulam
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 322 Issue 2 Pg. 646-53 (Aug 2007) ISSN: 0022-3565 [Print] United States
• PMID: 17478614 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Antineoplastic Agents
• Troponin T
• cannabidiol hydroxyquinone
• Cannabidiol
• Malondialdehyde
• Doxorubicin

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Blood Cell Count
• Body Weight (drug effects)
• Cannabidiol (analogs & derivatives, chemistry, pharmacology)
• Cell Line, Tumor
• Doxorubicin (chemistry, pharmacology)
• Echocardiography
• HT29 Cells
• Heart (drug effects, physiopathology)
• Humans
• Lipid Peroxidation (drug effects)
• Male
• Malondialdehyde (metabolism)
• Mice
• Mice, Inbred NOD
• Mice, Inbred Strains
• Mice, Nude
• Mice, SCID
• Molecular Structure
• Myocardium (metabolism, pathology)
• Neoplasms (blood, drug therapy, pathology)
• Protein Carbonylation (drug effects)
• Troponin T (blood)
• Xenograft Model Antitumor Assays