λ Phage Nanobioparticle Expressing Apoptin Efficiently Suppress Human Breast Carcinoma Tumor Growth In Vivo

Abstract

Using phages is a novel field of cancer therapy and phage nanobioparticles (NBPs) such as λ phage could be modified to deliver and express genetic cassettes into eukaryotic cells safely in contrast with animal viruses. Apoptin, a protein from chicken anemia virus (CAV) has the ability to specifically induce apoptosis only in carcinoma cells. We presented a safe method of breast tumor therapy via the apoptin expressing λ NBPs. Here, we constructed a λ ZAP-CMV-apoptin recombinant NBP and investigated the effectiveness of its apoptotic activity on BT-474, MDA-MB-361, SKBR-3, UACC-812 and ZR-75 cell lines that over-expressing her-2 marker. Apoptosis was evaluated via annexin-V fluorescent iso-thiocyanate/propidium iodide staining, flow-cytometric method and TUNEL assay. Transfection with NBPs carrying λ ZAP-CMV-apoptin significantly inhibited growth of all the breast carcinoma cell lines in vitro. Also nude mice model implanted BT-474 human breast tumor was successfully responded to the systemic and local injection of untargeted recombinant λ NBPs. The results presented here reveal important features of recombinant λ nanobioparticles to serve as safe delivery and expression platform for human cancer therapy.

Antitumor Effects of a Recombinant Baculovirus Displaying Anti-HER2 Scfv Expressing Apoptin in HER2 Positive SK-BR-3 Breast Cancer Cells

“…However, Apoptin has been shown to be able to induce the apoptosis in a variety of tumor cells [18], [18] and efficient delivery systems is are required to transfer Apoptin to cancer cells. Here we showed that the ability of BV-displaying anti-HER2 scFv to deliver Apoptin into breast cancer cells was demonstrated (Figure 7).…”

“…Several studies reported an antitumor effect of Apoptin in breast cancer cells. Shoae-Hassani and colleagues constructed a λ phage expressing the Apoptin which significantly inhibited growth of the various breast cancer cell lines in vitro [18]. AnoOther study also showed that HSA-mediated Apoptin infection was able to reduce the viability and induce the apoptosis in MCF-7 cells [41].…”

“…Apoptin (VP3) is an anti-cancer protein derived from chicken anemia virus (CAV) that induces the selective death in different cancer cell lines but not in normal cells. Apoptin tumor -specificity is associated with its ability to localize in the nuclei of transforming cells, whereas it is mainly found in the cytoplasm of normal cells [14,[18][19][20].…”

Human Gyrovirus Apoptin as a Potential Selective Anticancer Agent: An In Vitro Study

“…, March 2019, 25, 44-49 | 47 One of the most prominent features of CAV-Apoptin is its specific cytotoxicity in cancerous cells, as shown in many studies to date. [22][23][24] Despite extensive studies on CAV-Apoptin, HGV-Apoptin was discovered recently and its apoptotic effects has been evaluated on a few cell lines. In this study, we moved a step forward to show that HGV-Apoptin has cytotoxic effects on Non-small-cell lung carcinoma cell line A549, while it had no effects on non-cancerous human embryonic kidney cell line HEK-293.…”

Viral genes as oncolytic agents for cancer therapy

“…Further, modified phage nanobioparticles (NBPs) such as k phage can safely deliver and express the transgene into eukaryotic cells. A recombinant NBP (k ZAP-CMVapoptin) could inhibit growth of breast carcinoma cell lines in vitro and in BT-474 human breast tumor in the nude mice model in vivo [199].…”