Infection with oncolytic herpes simplex virus-1 induces apoptosis in neighboring human cancer cells: A potential target to increase anticancer activity Journal Article
| Authors: | Stanziale, S. F.; Petrowsky, H.; Adusumilli, P. S.; Ben-Porat, L.; Gonen, M.; Fong, Y. |
| Article Title: | Infection with oncolytic herpes simplex virus-1 induces apoptosis in neighboring human cancer cells: A potential target to increase anticancer activity |
| Abstract: | Purpose: The antitumor efficacy of a herpes simplex virus (HSV)-1 oncolytic virus depends on the cytotoxic effect of the virus, but also on viral replication and spread within the tumor. Apoptosis is considered a defense mechanism of infected cells that minimizes the spread of viral progeny by limiting cellular production of virus. We sought to determine whether oncolytic HSV-1 infection induces apoptosis in neighboring, uninfected cells and whether manipulation of apoptosis can increase viral replication and cytotoxicity. Experimental Design: NV1066 is an oncolytic HSV-1 mutant that contains the marker gene for enhanced green fluorescent protein. OCUM human gastric cancer cells were infected with NV1066 in vitro and inspected for apoptosis by Hoechst and terminal deoxynucleotidyltransfernse-mediated nick end labeling staining and for infection by expression of green fluorescence. Results: A significant increase in apoptosis was seen in cells infected by NV1066. More interestingly, a significant percentage (10%) of uninfected cells also proceeded to apoptosis. After NV1066 infection, cells were also treated with N-acetylcysteine (NAC), an inhibitor of apoptosis. By day 4 after infection, 2.7× more NV1066 was produced in cells exposed to NAC than in those not exposed to NV1066 (P = 0.04). NAC also increased tumor kill when administered with virus. Conclusions: These data suggest that NV1066 induces apoptosis in uninfected cocultured cells, potentially hindering propagation of viral progeny and concomitant tumor kill. Inhibition of apoptosis may improve the efficacy of oncolytic HSV-1 therapy. |
| Keywords: | controlled study; human cell; drug efficacy; flow cytometry; apoptosis; gene expression; green fluorescent protein; antineoplastic activity; cytotoxicity; in vitro study; cell line, tumor; luminescent proteins; gastrointestinal neoplasms; dactinomycin; stomach cancer; green fluorescent proteins; cytolysis; hoe 33342; herpesvirus 1, human; virus infection; virus replication; nick end labeling; herpes simplex virus 1; marker gene; in situ nick-end labeling; oncolysis; acetylcysteine; humans; human; priority journal; article |
| Journal Title: | Clinical Cancer Research |
| Volume: | 10 |
| Issue: | 9 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2004-05-01 |
| Start Page: | 3225 |
| End Page: | 3232 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-1083-3 |
| PROVIDER: | scopus |
| PUBMED: | 15131064 |
| DOI/URL: | |
| Notes: | Clin. Cancer Res. -- Cited By (since 1996):23 -- Export Date: 16 June 2014 -- CODEN: CCREF -- Source: Scopus |
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