title: In vitro and in vivo efficacy of non-psychoactive cannabidiol in neuroblastoma.
abstract: BACKGROUND
  Neuroblastoma (nbl) is one of the most common solid cancers in children. Prognosis in advanced nbl is still poor despite aggressive multimodality therapy. Furthermore, survivors experience severe long-term multi-organ sequelae. Hence, the identification of new therapeutic strategies is of utmost importance. Cannabinoids and their derivatives have been used for years in folk medicine and later in the field of palliative care. Recently, they were found to show pharmacologic activity in cancer, including cytostatic, apoptotic, and antiangiogenic effects.
  
  
  METHODS
  We investigated, in vitro and in vivo, the anti-nbl effect of the most active compounds in Cannabis, Δ(9)-tetrahydrocannabinol (thc) and cannabidiol (cbd). We set out to experimentally determine the effects of those compounds on viability, invasiveness, cell cycle distribution, and programmed cell death in human nbl SK-N-SH cells.
  
  
  RESULTS
  Both compounds have antitumourigenic activity in vitro and impeded the growth of tumour xenografts in vivo. Of the two cannabinoids tested, cbd was the more active. Treatment with cbd reduced the viability and invasiveness of treated tumour cells in vitro and induced apoptosis (as demonstrated by morphology changes, sub-G1 cell accumulation, and annexin V assay). Moreover, cbd elicited an increase in activated caspase 3 in treated cells and tumour xenografts.
  
  
  CONCLUSIONS
  Our results demonstrate the antitumourigenic action of cbd on nbl cells. Because cbd is a nonpsychoactive cannabinoid that appears to be devoid of side effects, our results support its exploitation as an effective anticancer drug in the management of nbl.
authors.affiliation: Pediatric Hemato-Oncology Research Laboratory, Sheba Cancer Research Center.
authors.forename: T
authors.initials: T
authors.lastname: Fisher
authors.affiliation: Pediatric Hemato-Oncology Research Laboratory, Sheba Cancer Research Center; Department of Pediatric Hemato-Oncology, The Edmond and Lily Safra Children's Hospital.
authors.forename: H
authors.initials: H
authors.lastname: Golan
authors.affiliation: Department of Pathology, The Chaim Sheba Medical Center, Tel-Hashomer, Israel;
authors.forename: G
authors.initials: G
authors.lastname: Schiby
authors.affiliation: Pediatric Stem Cell Research Institute, The Chaim Sheba Medical Center, Tel-Hashomer, Israel;
authors.forename: S
authors.initials: S
authors.lastname: PriChen
authors.affiliation: Institute for Drug Research, Hebrew University of Jerusalem, Jerusalem, Israel;
authors.forename: R
authors.initials: R
authors.lastname: Smoum
authors.affiliation: Pediatric Hemato-Oncology Research Laboratory, Sheba Cancer Research Center.
authors.forename: I
authors.initials: I
authors.lastname: Moshe
authors.affiliation: Cancer Research Center, The Chaim Sheba Medical Center, Tel-Hashomer, Israel;
authors.forename: N
authors.initials: N
authors.lastname: Peshes-Yaloz
authors.affiliation: Cancer Research Center, The Chaim Sheba Medical Center, Tel-Hashomer, Israel;
authors.forename: A
authors.initials: A
authors.lastname: Castiel
authors.affiliation: Pediatric Hemato-Oncology Research Laboratory, Sheba Cancer Research Center; Department of Pediatric Hemato-Oncology, The Edmond and Lily Safra Children's Hospital.
authors.forename: D
authors.initials: D
authors.lastname: Waldman
authors.affiliation: The Lautenberg Center for General and Tumour Immunology, Hebrew University of Jerusalem, Jerusalem, Israel;
authors.forename: R
authors.initials: R
authors.lastname: Gallily
authors.affiliation: Institute for Drug Research, Hebrew University of Jerusalem, Jerusalem, Israel;
authors.forename: R
authors.initials: R
authors.lastname: Mechoulam
authors.affiliation: Department of Pediatric Hemato-Oncology, The Edmond and Lily Safra Children's Hospital; Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Toren
keywords: Neuroblastoma; apoptosis; cannabidiol; non-psychoactive cannabinoids; tumour xenograft models; Δ9-tetrahydrocannabinol