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Control by the endogenous cannabinoid system of ras oncogene-dependent tumor growth.
FASEB J. 2001 Dec; 15(14):2745-7.FJ

Abstract

We investigated the effect of 2-methyl-arachidonyl-2'-fluoro-ethylamide (Met-F-AEA), a stable analog of the endocannabinoid anandamide, on a rat thyroid epithelial cell line (FRTL-5) transformed by the K-ras oncogene, and on epithelial tumors derived from these cells. Met-F-AEA effect in vivo was evaluated in a nude mouse xenograft model, where K-ras-transformed (KiMol) cells were implanted subcutaneously. Met-F-AEA (0.5 mg/kg/dose) induced a drastic reduction in tumor volume. This effect was inhibited by the CB1 receptor antagonist SR141716A (0.7 mg/kg/dose) and was accompanied by a strong reduction of K-ras activity. Accordingly, KiMol cells and tumors express CB1 receptors. Met-F-AEA inhibited (IC50 ~5 mM) the proliferation in vitro and the transition to the S phase of KiMol cells and it reduced K-ras activity; these effects were antagonized by SR141716A. Met-F-AEA cytostatic action was significantly smaller in nontransformed FRTL-5 cells than in KiMol cells. Met-F-AEA treatment exerted opposite effects on the expression of CB1 receptors in KiMol and FRTL-5 cells, with a strong up-regulation in the former case and a suppression in nontransformed cells. The data suggest that: 1) Met-F-AEA inhibits ras oncogene-dependent tumor growth in vivo through CB1 cannabinoid receptors; and 2) responsiveness of FRTL-5 cells to endocannabinoids depends on whether or not they are transformed by K-ras.

Authors+Show Affiliations

Dipartimento di Scienze Farmaceutiche, Università degli Studi di Salerno, via Ponte Don Melillo, 84084 Fisciano, Salerno, Italy. maubiful@unina.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11687506

Citation

Bifulco, M, et al. "Control By the Endogenous Cannabinoid System of Ras Oncogene-dependent Tumor Growth." FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, vol. 15, no. 14, 2001, pp. 2745-7.
Bifulco M, Laezza C, Portella G, et al. Control by the endogenous cannabinoid system of ras oncogene-dependent tumor growth. FASEB J. 2001;15(14):2745-7.
Bifulco, M., Laezza, C., Portella, G., Vitale, M., Orlando, P., De Petrocellis, L., & Di Marzo, V. (2001). Control by the endogenous cannabinoid system of ras oncogene-dependent tumor growth. FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, 15(14), 2745-7.
Bifulco M, et al. Control By the Endogenous Cannabinoid System of Ras Oncogene-dependent Tumor Growth. FASEB J. 2001;15(14):2745-7. PubMed PMID: 11687506.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Control by the endogenous cannabinoid system of ras oncogene-dependent tumor growth. AU - Bifulco,M, AU - Laezza,C, AU - Portella,G, AU - Vitale,M, AU - Orlando,P, AU - De Petrocellis,L, AU - Di Marzo,V, Y1 - 2001/10/29/ PY - 2001/11/1/pubmed PY - 2002/1/16/medline PY - 2001/11/1/entrez SP - 2745 EP - 7 JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JO - FASEB J VL - 15 IS - 14 N2 - We investigated the effect of 2-methyl-arachidonyl-2'-fluoro-ethylamide (Met-F-AEA), a stable analog of the endocannabinoid anandamide, on a rat thyroid epithelial cell line (FRTL-5) transformed by the K-ras oncogene, and on epithelial tumors derived from these cells. Met-F-AEA effect in vivo was evaluated in a nude mouse xenograft model, where K-ras-transformed (KiMol) cells were implanted subcutaneously. Met-F-AEA (0.5 mg/kg/dose) induced a drastic reduction in tumor volume. This effect was inhibited by the CB1 receptor antagonist SR141716A (0.7 mg/kg/dose) and was accompanied by a strong reduction of K-ras activity. Accordingly, KiMol cells and tumors express CB1 receptors. Met-F-AEA inhibited (IC50 ~5 mM) the proliferation in vitro and the transition to the S phase of KiMol cells and it reduced K-ras activity; these effects were antagonized by SR141716A. Met-F-AEA cytostatic action was significantly smaller in nontransformed FRTL-5 cells than in KiMol cells. Met-F-AEA treatment exerted opposite effects on the expression of CB1 receptors in KiMol and FRTL-5 cells, with a strong up-regulation in the former case and a suppression in nontransformed cells. The data suggest that: 1) Met-F-AEA inhibits ras oncogene-dependent tumor growth in vivo through CB1 cannabinoid receptors; and 2) responsiveness of FRTL-5 cells to endocannabinoids depends on whether or not they are transformed by K-ras. SN - 1530-6860 UR - https://www.unboundmedicine.com/medline/citation/11687506/Control_by_the_endogenous_cannabinoid_system_of_ras_oncogene_dependent_tumor_growth_ L2 - https://doi.org/10.1096/fj.01-0320fje DB - PRIME DP - Unbound Medicine ER -