![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
CHEMOTHERAPY, ANTIBIOTICS, AND GENE THERAPY
Endocannabinoid Research Group, Istituto di Chimica Biomolecolare (A.L., A.S.M., K.S., I.M., V.D.M.), and Istituto di Cibernetica (A.S.M., L.D.P.), Consiglio Nazionale delle Ricerche Pozzuoli, Italy; Dipartimento di Biologia e Patologia Cellulare e Molecolare "L. Califano", Università di Napoli "Federico II", Napoli, Italy (S.P., C.L., G.P., M.B.); and Dipartimento di Scienze Farmaceutiche, Università degli Studi di Salerno, Fisciano, Italy (S.P., M.B.)
9-Tetrahydrocannabinol (THC) exhibits antitumor effects on various cancer cell types, but its use in chemotherapy is limited by its psychotropic activity. We investigated the antitumor activities of other plant cannabinoids, i.e., cannabidiol, cannabigerol, cannabichromene, cannabidiol acid and THC acid, and assessed whether there is any advantage in using Cannabis extracts (enriched in either cannabidiol or THC) over pure cannabinoids. Results obtained in a panel of tumor cell lines clearly indicate that, of the five natural compounds tested, cannabidiol is the most potent inhibitor of cancer cell growth (IC50 between 6.0 and 10.6 µM), with significantly lower potency in noncancer cells. The cannabidiol-rich extract was equipotent to cannabidiol, whereas cannabigerol and cannabichromene followed in the rank of potency. Both cannabidiol and the cannabidiol-rich extract inhibited the growth of xenograft tumors obtained by s.c. injection into athymic mice of human MDA-MB-231 breast carcinoma or rat v-K-ras-transformed thyroid epithelial cells and reduced lung metastases deriving from intrapaw injection of MDA-MB-231 cells. Judging from several experiments on its possible cellular and molecular mechanisms of action, we propose that cannabidiol lacks a unique mode of action in the cell lines investigated. At least for MDA-MB-231 cells, however, our experiments indicate that cannabidiol effect is due to its capability of inducing apoptosis via: direct or indirect activation of cannabinoid CB2 and vanilloid transient receptor potential vanilloid type-1 receptors and cannabinoid/vanilloid receptor-independent elevation of intracellular Ca2+ and reactive oxygen species. Our data support the further testing of cannabidiol and cannabidiol-rich extracts for the potential treatment of cancer.
Address correspondence to: Dr. Vincenzo Di Marzo, Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Via Campi Flegrei 34, 80078 Pozzuoli, Napoli, Italy. E-mail: vdimarzo{at}icmib.na.cnr.it
This article has been cited by other articles:
|
|
 |
|
  M. Bifulco, A. M. Malfitano, S. Pisanti, and C. Laezza Endocannabinoids in endocrine and related tumours Endocr. Relat. Cancer, June 1, 2008; 15(2): 391 - 408. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. De Petrocellis, V. Vellani, A. Schiano-Moriello, P. Marini, P. C. Magherini, P. Orlando, and V. Di Marzo Plant-Derived Cannabinoids Modulate the Activity of Transient Receptor Potential Channels of Ankyrin Type-1 and Melastatin Type-8 J. Pharmacol. Exp. Ther., June 1, 2008; 325(3): 1007 - 1015. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Sarfaraz, V. M. Adhami, D. N. Syed, F. Afaq, and H. Mukhtar Cannabinoids for Cancer Treatment: Progress and Promise Cancer Res., January 15, 2008; 68(2): 339 - 342. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. D. McAllister, R. T. Christian, M. P. Horowitz, A. Garcia, and P.-Y. Desprez Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells Mol. Cancer Ther., November 1, 2007; 6(11): 2921 - 2927. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
