Voacamine Abstract: Antimalarial drug extracted from Peschiera fuchsiaefolia

In our previous studies, voacamine, a bisindolic alkaloid extracted from Peschiera fuchsiaefolia, was examined for its possible capability of  enhancing the cytotoxic  effect of doxorubicin (DOX) on multidrug resistant (MDR) human osteosarcoma  cells (U-2 OS-R). Voacamine induced in resistant cells a significant increase of drug  retention and intranuclear location which became comparable to those observed   in the parental sensitive  counterparts (U-2 OS-WT). In the present study, the cell  survival analysis and the electron microscopic observations confirmed the evident   cytotoxicity of DOX on MDR cells after pre-treatment with the plant extract.  

Moreover, an increase of the reactivity of P-glycoprotein (P-gp) with the  monoclonal antibody UIC2, which recognizes an epitope of the drug transporter in  its functional conformation, was revealed, demonstrating that voacamine is a substrate of P-gp, thus acting as a competitive antagonist of the cytotoxic agent. 

Moreover, to investigate if the enhancement of the cytotoxic effect induced by  voacamine could be due to an apoptotic process, we carried out the analysis of  cell morphology after Hoechst staining and the quantification of apoptosis by   Annexin V-FITC assay. These evaluations showed a very low rate of apoptosis in U-2   OS-R cells treated with voacamine and DOX given in association. In addition, the  combined treatment induced ultrastructural modifications suggestive of  autophagic cell death. In particular, transmission electron microscopy  observations revealed the presence of numerous lysosomes and the formation of a  large number of autophagosomes containing residual digested material. 

In conclusion, these findings seem to indicate that voacamine is capable of 
enhancing the cytotoxic effect of DOX on MDR cells by favouring a lethal   autophagic process.

No conclusion  about the side effects of voacamine have been released. Check the Voacamine Side Effects tracking page for any drug alerts about this product.