A Novel Double-Enhanced Suicide Gene Therapy in a Colon Cancer Cell Line Mediated by Gef and Apoptin

Abstract

Double-suicide gene therapy based on gef and apoptin genes may be a candidate for the development of new colon cancer strategies, and further studies are warranted to establish the usefulness of double-suicide gene therapy in vivo.

Enhancement of Tumor Cell Death by Combining gef Gene Mediated Therapy and New 1,4-Benzoxazepin-2,6-Dichloropurine Derivatives in Breast Cancer Cells

“…However, the combined expression of gef gene and different drugs induced a marked increase on necrotic cells. This phenomenon was also observed after the co-expression of the gef and apoptin genes in colon cancer cells ( Boulaiz et al, 2014 ). This necrosis should be classified as post-apoptotic secondary necrosis what is the natural outcome of the complete apoptotic program as described by Silva (2010) .…”

“…However, the effective doses (10 μM) were much higher than those necessary to induce a similar effect to that obtained by the FC-30b2, FC-29c, and bozepinib compounds ( Prados et al, 2010 ). In addition, cell viability was reduced by 65.13% when gef and apoptin were synergistically co-expressed in colon DLD-1 treated cells after 10 days of treatment with doxycycline, while only the expression of gef or apoptin gene alone obtained a reduction of 35.9% and 47.95%, respectively ( Boulaiz et al, 2014 ). The fact that the potentiation of the effect of combined therapy on cell proliferation is uncovered after a 6 days treatment was observed also after gef and apoptin genes co-expression and may be due of the needing for a target amount of gef protein in the tumor cells to trigger cell death ( Boulaiz et al, 2014 ).…”

“…In addition, cell viability was reduced by 65.13% when gef and apoptin were synergistically co-expressed in colon DLD-1 treated cells after 10 days of treatment with doxycycline, while only the expression of gef or apoptin gene alone obtained a reduction of 35.9% and 47.95%, respectively ( Boulaiz et al, 2014 ). The fact that the potentiation of the effect of combined therapy on cell proliferation is uncovered after a 6 days treatment was observed also after gef and apoptin genes co-expression and may be due of the needing for a target amount of gef protein in the tumor cells to trigger cell death ( Boulaiz et al, 2014 ). The requirement of a critical concentration of gef protein to trigger cell death was reported in prokaryotic cells ( Ronchel et al, 1998 ).…”

Apoptin as a Tumor-Specific Therapeutic Agent: Current Perspective on Mechanism of Action and Delivery Systems

“…In addition to direct delivery to cancer cell lines and to xenografts of human tumors in mice through intra-tumoral route, effective Apoptin delivery through adenovirus has been achieved via intraperitoneal, subcutaneous, or intravenous injections against xenogeneic tumors in mice ( Pietersen et al, 1999 ). Boulaiz et al (2014) have used a retroviral-mediated conditional gene expression system to deliver Apoptin to a colon cancer cell line. A recombinant vaccinia virus expressing Apoptin has been reported to involve cytoskeletal changes which result in the replacement of epithelioid carcinoma xenograft tissue with a filamentous material ( Kochneva et al, 2014 ).…”

“…Combined administration of Apoptin and gef kills cancer cells by inducing pore formation, followed by necrosis. The combination has been reported to decrease cell viability, increase necrosis, and induce apoptosis in colon cancer cells more effectively than either of the two genes alone ( Boulaiz et al, 2014 ; Caceres et al, 2019 ). Melanoma differentiation-associated gene-7 (MDA7) is an anti-tumor gene that has been found to suppress monolayer growth and anchorage dependence of various cancer cell lines, and inhibit tumor growth in tumor xenografts in mice ( Mhashilkar et al, 2001 ).…”