Voacamine modulates the sensitivity to doxorubicin of resistant osteosarcoma and melanoma cells and does not induce toxicity in normal fibroblasts.
In previous studies it has been demonstrated that the plant alkaloid voacamine (1), used at noncytotoxic concentrations, enhanced the cytotoxicity of doxorubicin and exerted a chemosensitizing effect on cultured multidrug-resistant (MDR) U-2 OS-DX osteosarcoma cells. The in vitro investigations reported herein gave the following results: (i) the chemosensitizing effect of 1, in terms of drug accumulation and cell survival, was confirmed using SAOS-2-DX cells, another MDR osteosarcoma cell line; (ii) compound 1 enhanced the cytotoxic effect of doxorubicin also on the melanoma cell line Me30966, intrinsically drug resistant and P-glycoprotein-negative; (iii) at the concentrations used to sensitize tumor cells, 1 was not cytotoxic to normal cells (human fibroblasts). These findings suggest possible applications of voacamine (1) in integrative oncologic therapies against resistant tumors.
Department of Technology and Health, Italian National Institute of Health , Rome, Italy.
Maria
M
Condello
Dario
D
Cosentino
Silvia
S
Corinti
Gabriella
G
Di Felice
Giuseppina
G
Multari
Francesca Romana
FR
Gallo
Giuseppe
G
Arancia
Stefania
S
Meschini
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism; D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001859:Bone Neoplasms / Q000188:drug therapy*; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005347:Fibroblasts / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007050:Ibogaine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D008545:Melanoma / Q000188:drug therapy*; D015394:Molecular Structure; D012516:Osteosarcoma / Q000188:drug therapy*
D018435:ATP Binding Cassette Transporter, Subfamily B; D000470:Alkaloids; C005891:voacamine; D007050:Ibogaine; D004317:Doxorubicin