The Effects of Curcumin and Flavokavain B on the Oncolytic Activity of Vesicular Stomatitis Virus

A promising cancer treatment modality is the use of oncolytic viruses to kill cancer cells. One virus that is currently being studied as an oncolytic agent is vesicular stomatitis virus (VSV). We are interested in developing the rM51R-M virus, a matrix (M) protein mutant of VSV, as a candidate oncolytic agent due to its capacity to kill cancer cells and its low virulence in vivo; however, prostate cancer cell lines like PC-3 are resistant to infection. Studies have shown that the transcription factor NF-kB is constitutively active in PC-3 cells, suggesting a role for the induction of the antiviral immune response. We hypothesize that the inhibition of NF-kB in cancer cells will render them susceptible to VSV. Our goal is to determine the ability of natural compounds (flavokavain B and curcumin), which inhibit NF-kB, to promote VSV induced oncolysis. Our results show that curcumin potentiated VSV-induced oncolysis after 24 hours post-infection; however flavokavain B did not. Neither curcumin nor flavokavain B decreased viral protein expression. Additionally, pretreatment of cells with curcumin prior to infection led to a decrease in expression of the antiapoptotic protein, BCL-XL. These results suggest that natural products have the potential to synergize with oncolytic VSV therapies.