Voacamine modulates the sensitivity to doxorubicin of resistant osteosarcoma and melanoma cells and does not induce toxicity in normal fibroblasts.

Abstract

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.

• Authors: Maria Condello, Dario Cosentino, Silvia Corinti, Gabriella Di Felice, Giuseppina Multari, Francesca Romana Gallo, Giuseppe Arancia, Stefania Meschini
• Journal: Journal of natural products (J Nat Prod) Vol. 77 Issue 4 Pg. 855-62 (Apr 25 2014) ISSN: 1520-6025 [Electronic] United States
• PMID: 24720452 (Publication Type: Journal Article)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B
• Alkaloids
• voacamine
• Ibogaine
• Doxorubicin

Topics

• ATP Binding Cassette Transporter, Subfamily B (metabolism)
• Alkaloids (chemistry, pharmacology)
• Apoptosis (drug effects)
• Bone Neoplasms (drug therapy)
• Cell Survival (drug effects)
• Doxorubicin (pharmacology)
• Drug Resistance, Multiple (drug effects)
• Drug Resistance, Neoplasm (drug effects)
• Fibroblasts (metabolism)
• Fluorescent Antibody Technique
• Humans
• Ibogaine (analogs & derivatives, chemistry, pharmacology)
• Melanoma (drug therapy)
• Molecular Structure
• Osteosarcoma (drug therapy)