Open AccessVoacamine Modulates the Sensitivity to Doxorubicin of Resistant Osteosarcoma and Melanoma Cells and Does Not Induce Toxicity in Normal Fibroblasts
Author(s) -
Maria Condello,
Dario Cosentino,
Silvia Corinti,
Gabriella Di Felice,
Giuseppina Multari,
Francesca Romana Gallo,
Giuseppe Arancia,
Stefania Meschini
Publication year - 2014
Publication title -
journal of natural products
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.976
H-Index - 139
eISSN - 1520-6025
pISSN - 0163-3864
DOI - 10.1021/np400950h
Subject(s) - doxorubicin , osteosarcoma , cytotoxicity , cytotoxic t cell , multiple drug resistance , cell culture , p glycoprotein , in vitro , cancer research , pharmacology , melanoma , medicine , toxicity , cell , biology , chemotherapy , drug resistance , chemistry , biochemistry , microbiology and biotechnology , genetics
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.
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