title: Curcumin promotes the oncoltyic capacity of vesicular stomatitis virus for the treatment of prostate cancers.
abstract: Vesicular stomatitis virus (VSV) matrix (M) protein mutants have been studied as oncolytic agents due to their capacity to effectively kill cancer cells while exhibiting low virulence in vivo. Despite encouraging results, many cancer cells maintain resistance to oncolytic VSV mutants in part due to residual antiviral responses. We sought to determine whether combination of VSV with natural agents with anti-tumor properties, such as curcumin, resveratrol, and flavokavain B, would enhance tumor cell killing in a prostate cancer model. Our results revealed that pretreatment with curcumin potentiated VSV-induced oncolysis of PC-3 prostate cancer cells in cell culture and in a mouse model of prostate cancer. The ability of curcumin to synergize with VSV in PC-3 cells correlated with a cumulative decrease in the expression of the anti-apoptotic protein, Bcl-xl, and in the phosphorylation of NF-κB. Although curcumin did not impact the expression of type I IFN in infected cells, it inhibited the phosphorylation and activation of STAT1, a key player in the IFN response pathway, leading to an overall increase in virus-infected cells. These results suggest that curcumin sensitizes prostate cancer cells to the oncolytic effects of VSV by modulating antiviral responses and components of the intrinsic apoptotic pathway.
authors.affiliation: Department of Biology, Appalachian State University, Boone, NC 28608, United States.
authors.forename: Dylan J
authors.initials: DJ
authors.lastname: Fehl
authors.affiliation: Department of Biology, Appalachian State University, Boone, NC 28608, United States. Electronic address: ahmedm@appstate.edu.
authors.forename: Maryam
authors.initials: M
authors.lastname: Ahmed
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D050130:Oncolytic Virotherapy / Q000379:methods; D050504:Oncolytic Viruses / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy / Q000821:virology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics*; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays
chemical_list: D007370:Interferon Type I; D016328:NF-kappa B; D051057:Proto-Oncogene Proteins c-akt; D003474:Curcumin
keywords: Apoptosis; Curcumin; Oncolytic vesicular stomatitis virus; Prostate cancer; Type I interferon