title: Selective, nontoxic CB(2) cannabinoid o-quinone with in vivo activity against triple-negative breast cancer.
abstract: Triple-negative breast cancer (TNBC) represents a subtype of breast cancer characterized by high aggressiveness. There is no current targeted therapy for these patients whose prognosis, as a group, is very poor. Here, we report the synthesis and evaluation of a potent antitumor agent in vivo for this type of breast cancer designed as a combination of quinone/cannabinoid pharmacophores. This new compound (10) has been selected from a series of chromenopyrazolediones with full selectivity for the nonpsychotropic CB2 cannabinoid receptor and with efficacy in inducing death of human TNBC cell lines. The dual concept quinone/cannabinoid was supported by the fact that compound 10 exerts antitumor effect by inducing cell apoptosis through activation of CB2 receptors and through oxidative stress. Notably, it did not show either cytotoxicity on noncancerous human mammary epithelial cells nor toxic effects in vivo, suggesting that it may be a new therapeutic tool for the management of TNBC.
authors: Instituto de Química Médica, CSIC , Calle Juan de la Cierva 3, 28006 Madrid, Spain.
authors: Paula
authors: P
authors: Morales
authors: Sandra
authors: S
authors: Blasco-Benito
authors: Clara
authors: C
authors: Andradas
authors: María
authors: M
authors: Gómez-Cañas
authors: Juana María
authors: JM
authors: Flores
authors: Pilar
authors: P
authors: Goya
authors: Javier
authors: J
authors: Fernández-Ruiz
authors: Cristina
authors: C
authors: Sánchez
authors: Nadine
authors: N
authors: Jagerovic
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001578:Benzopyrans / Q000737:chemistry / Q000494:pharmacology*; D016227:Benzoquinones / Q000737:chemistry*; D015153:Blotting, Western; D001940:Breast / Q000166:cytology / Q000187:drug effects*; D002186:Cannabinoids / Q000737:chemistry*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D043885:Receptor, Cannabinoid, CB2 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: C000598569:7-(1',1'-dimethylheptyl)-1-ethyl-1,4-dihydro-4,4-dimethylchromeno(4,3-c)pyrazole-8,9-dione; D000970:Antineoplastic Agents; D001578:Benzopyrans; D016227:Benzoquinones; D002186:Cannabinoids; D011720:Pyrazoles; D012333:RNA, Messenger; D043885:Receptor, Cannabinoid, CB2; C004532:quinone