Moringa oleifera and vesicular stomatitis virus: A combination approach for the treatment of cervical cancers

Abstract

Vesicular stomatitis virus (VSV) is a promising oncolytic agent due to its natural ability to target and kill a variety of susceptible cancer cells. However, some cancer cells exhibit inherent resistance to VSV and thus, strategies to potentiate treatment responses are currently being investigated. This study seeks to determine whether the oncolytic activity of VSV may be augmented by treating cells with natural compounds with known anti-cancer properties, such as Moringa oleifera (MO). Five different extracts from the leaves of MO were prepared and tested for their biological activities against cervical cancer cells in conjunction with VSV. In addition, the mechanism of oncolytic VSV and MO targeting and killing of cancer cells was analyzed through measurement of protein levels and activation status of key apoptotic and antiviral factors. Of the five extracts of MO examined (aqueous, butanolic, ethanolic, hydroethanolic, and methanolic), the ethanolic extract inhibited the proliferation of C4-II and HeLa cervical cancer cells. This inhibition correlated with decreased levels of NF-κB and Bcl-xL in these cells. In conjunction with VSV, the ethanolic extract enhanced the ability of a wild-type strain of VSV (rwt virus) to kill cells, perhaps by inducing expression of the pro-apoptotic protein, Bax. The methanolic extract promoted killing of SiHa cervical cancer cells by a M (matrix) protein mutant strain of VSV, but did not affect the proliferation of cells. Furthermore, STAT1 levels decreased in VSV-infected cells pretreated with MO suggesting that MO may inhibit induction of an antiviral response and promote VSV replication in these cells prior to immune detection. These results indicate that MO may synergize with VSV for the treatment of cervical cancers through modulation of pathways involved in cell proliferation, apoptosis and antiviral responses.