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Research ArticleCHEMOTHERAPY, ANTIBIOTICS, AND GENE THERAPY

A Cannabinoid Anticancer Quinone, HU-331, Is More Potent and Less Cardiotoxic Than Doxorubicin: A Comparative in Vivo Study

Natalya M. Kogan, Michael Schlesinger, Maximilian Peters, Gergana Marincheva, Ronen Beeri and Raphael Mechoulam
Journal of Pharmacology and Experimental Therapeutics August 2007, 322 (2) 646-653; DOI: https://doi.org/10.1124/jpet.107.120865
Natalya M. Kogan
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Michael Schlesinger
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Maximilian Peters
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Gergana Marincheva
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Ronen Beeri
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Raphael Mechoulam
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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.

Footnotes

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

  • doi:10.1124/jpet.107.120865.

  • ABBREVIATIONS: LVEDD, left ventricular end diastolic diameter; LVESD, left ventricular end systolic diameter; IVSWD, interventricular septal wall diameter; LV, left ventricular; cTnT, cardiac troponin T; Abs, absorbance; MDA, malondialdehyde; EF, ejection fraction; FS, fractional shortening; HU-331, 3S,4R-p-benzoquinone-3-hydroxy-2-p-mentha-(1,8)-dien-3-yl-5-pentyl.

    • Received February 1, 2007.
    • Accepted April 26, 2007.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 322 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 322, Issue 2
1 Aug 2007
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Research ArticleCHEMOTHERAPY, ANTIBIOTICS, AND GENE THERAPY

A Cannabinoid Anticancer Quinone, HU-331, Is More Potent and Less Cardiotoxic Than Doxorubicin: A Comparative in Vivo Study

Natalya M. Kogan, Michael Schlesinger, Maximilian Peters, Gergana Marincheva, Ronen Beeri and Raphael Mechoulam
Journal of Pharmacology and Experimental Therapeutics August 1, 2007, 322 (2) 646-653; DOI: https://doi.org/10.1124/jpet.107.120865

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Research ArticleCHEMOTHERAPY, ANTIBIOTICS, AND GENE THERAPY

A Cannabinoid Anticancer Quinone, HU-331, Is More Potent and Less Cardiotoxic Than Doxorubicin: A Comparative in Vivo Study

Natalya M. Kogan, Michael Schlesinger, Maximilian Peters, Gergana Marincheva, Ronen Beeri and Raphael Mechoulam
Journal of Pharmacology and Experimental Therapeutics August 1, 2007, 322 (2) 646-653; DOI: https://doi.org/10.1124/jpet.107.120865
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