Tumor-suppressive effects by adenovirus-mediated mda-7 gene transfer in non-small cell lung cancer cell in vitro

Saeki, Tomoyuki; Mhashilkar, Abner M.; Chada, Sunil; Branch, Cynthia D.; Roth, Jack A.; Ramesh, Rajagopal

doi:10.1038/sj.gt.3301330

Cited by 147 publications

(198 citation statements)

References 12 publications

Supporting

Mentioning

187

Contrasting

Unclassified

Order By: Relevance

“…Differences in tumor size were analyzed for significance by the Student's t-test. Enhanced in vitro growth inhibitory and cytotoxic activity of Ad-mda7 and Herceptin in Her-2 þ breast cancer cells The antiproliferative effects of Ad-mda7 in various cancer cell types have been demonstrated in previous studies; [16][17][18][19][20][21][22][24][25][26][27][28][29][30][31][32][33][34]36 and the relevance of these findings to the clinical setting is supported by in vivo lung and breast xenograft models. 17,21 To corroborate that the Her-2 receptors expressed by the breast cancer cells are functional, we evaluated cell death in MDA-MB-453 and MCF-7 lines treated with increasing amounts of Herceptin (0-100 mg/ ml).…”

Section: Discussionmentioning

confidence: 80%

“…[16][17][18] Studies using adenoviral-mediated mda-7 (Ad-mda7) have demonstrated that adenoviral-mediated overexpression of mda-7 has tumor-selective growth inhibitory, antiangiogenic and proapoptotic properties both, in vitro and in vivo. [18][19][20][21][22][23]38 It is now known that mda-7 activates various signaling pathways in a cell-type-specific manner, and that these pathways ultimately converge on mitochondrial destruction and induction of apoptosis. 21,22,[24][25][26][27][28][29][30] However, in spite of its clear tumor-suppressive effects, the mechanisms by which Ad-mda7 induces cytotoxicity have not been fully characterized.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Combinatorial synergy induced by adenoviral-mediated mda-7 and Herceptin in Her-2+ breast cancer cells

et al. 2006

Self Cite

View full text Add to dashboard Cite

The melanoma differentiation-associated gene-7 (mda-7) is a member of the interleukin-10 cytokine family and a novel tumor suppressor gene. Adenoviral-mediated mda-7 (Ad-mda7) gene transfer has tumor-specific growth inhibitory and proapoptotic effects in a broad spectrum of cancer cells. In breast cancer cells, adenoviral-induced mda-7 expression triggers antiproliferative effects by downregulation of survival signals, such as Bcl-2 and Akt. The anti-human epidermal growth factor receptor-2 (Her-2) monoclonal antibody, Trastuzumab (Herceptin), increases the sensitivity of Her-2/neu-overexpressing breast cancer cells to chemotherapeutic agents and radiotherapy. In this study, we evaluate the effects of treatment with Ad-mda7 and Herceptin combination therapy in a panel of Her-2/neu-overexpressing cell lines, and in established tumors in nude mice. Compared to individual treatments, the combination of Ad-mda7 and Herceptin elicits supra-additive antitumor activity in Her-2/neuoverexpressing tumor cell lines: increased cell death, cell cycle block and apoptosis. The Ad-mda7 and Herceptin interaction was shown to be synergistic by isobologram analysis. Ad-mda7 does not alter cell surface Her-2/neu levels, but the combination of Ad-mda7 þ Herceptin results in increased expression of cell surface E-cadherin with concomitant translocation of b-catenin from the nucleus to the cell membrane. In vivo, the combination of Ad-mda7 and Herceptin showed significantly increased antitumor activity (Po0.003) against Her-2/neu-overexpressing tumors. These data suggest that the combination of Ad-mda7 with Herceptin may be a novel therapy for breast cancer patients whose tumors overexpress Her-2/neu. The observed synergistic effect may improve treatment options for otherwise poorly responsive, Her-2-positive, breast cancer patients. Cancer Gene Therapy (2006) 13, 958-968.

show abstract

Section: Discussionmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Combinatorial synergy induced by adenoviral-mediated mda-7 and Herceptin in Her-2+ breast cancer cells

et al. 2006

Self Cite

View full text Add to dashboard Cite

show abstract

“…The most recent publication from the same group showed that maximum mda-7 promoter activity requires 2 protein kinase C (PKC)-activated transcription factor AP-1 sites and 3 growth arrest and terminal differentiation specific transcription factor c/EBP sites for human melanoma differentiation. 6 Analyzing cell cycle effects, 7 showed that overexpression of mda-7 results in inhibition of cell proliferation and G2/M cell cycle arrest in nonsmall cell lung cancer cells in vitro. In the present study, we have also demonstrated that Ad-mda-7 infection of melanoma cells significantly suppressed cell proliferation by modulating a pathway-mediated via G2/M cell cycle arrest and inhibiting entry into S phase of the cell cycle.…”

Section: Discussionmentioning

confidence: 99%

“…Data now also exist to support a pro-apoptotic role for MDA-7 in cancer cells. 3,4,7 Infection with Ad-mda-7 has been reported to increase production of BAX 8 in breast, colorectal and nonsmall cell lung cancer cells and induce greater BAX/BCL2 ratios in breast carcinoma cells. 3 BAX protein has been proposed to induce channel formation in mitochondria, regulated by BCL-2 protein, resulting in the release of cytochrome c and caspase 9 and contributing to cell death.…”

Section: Discussionmentioning

confidence: 99%

Down-regulated melanoma differentiation associated gene (mda-7) expression in human melanomas

et al. 2001

View full text Add to dashboard Cite

The melanoma differentiation associated gene-7 (mda-7) has a potential inhibitory role in melanoma progression, although the mechanisms underlying this effect are still unknown. mda-7 mRNA has been found to be present at higher levels in cultured normal melanocytes compared with metastatic melanoma cell lines. Furthermore, levels of mda-7 message have shown an inverse correlation with melanoma progression in human tumor samples, suggesting that mda-7 may be a novel tumor suppressor gene. We have designed this study to investigate MDA-7 protein expression in different stages of melanoma progression and to examine its antiproliferative effects in vitro. Our data demonstrate that MDA-7 protein can be found in normal melanocytes and early stage melanomas. It is also observed in smooth muscle cells in the skin. However, in keeping with a possible role as a tumor suppressor, MDA-7 expression is decreased in more advanced melanomas, with nearly undetectable levels in metastatic disease. We also investigated antitumor effects of overexpressed MDA-7 on human melanoma cells in vitro. A feature of malignant tumors that is considered therapeutically exploitable is the loss of cellular differentiation. This has lead to a search for tissue-specific differentiation factors that might be reintroduced into tumors in order to modify their growth and ability to metastasize. In the case of melanoma, several unique genes have been isolated by Jiang et al. 1 from a melanoma cell line induced to differentiate by interferon-␤ and mezerein. One of the most interesting and promising of these genes is the melanoma differentiation associated gene-7 (mda-7). Since its initial isolation from melanoma cells and subsequent molecular characterization, the mda-7 gene and MDA-7 protein have been studied in numerous other tumor types, some of which have included carcinoma of the lung, breast, prostate and cervix. 2 Experiments using an adenovirus/mda-7 vector construct (Ad-mda-7) to infect normal and malignant cells have consistently demonstrated growth-inhibitory effects on various tumor types, but no inhibitory effects on normal cells. 3,4 These findings have prompted the development of the Ad-mda-7 as a potential therapeutic agent, and plans for a phase I clinical trial are under way. Although the initial description of mda-7 occurred in melanoma, most of the clinically relevant research has focused on the more prevalent malignancies. Our results demonstrate that Ad-mda-7 induces apoptosis and G2/M cell cycle arrest in melanoma cellsOur laboratory has an ongoing interest in the development of prognostic tools and therapeutic interventions for advanced melanoma. We have therefore undertaken a study to better define the significance of MDA-7 in this disease. We describe in this paper our data from human tumors and cell lines demonstrating that MDA-7 protein can be found in normal melanocytes, early stage melanomas and smooth muscle cells. However, in keeping with a role as a tumor suppressor, MDA-7 expression is decreased in more advanced melanom...

show abstract

“…Earlier studies showed that expression of IL-24 by plasmid or replication-defective adenovirus that harbored IL-24 suppressed cell growth and induced apoptosis in a wide variety of cancer cell lines, including melanoma, breast, lung, cervix, colon and prostate carcinomas, but not normal cells. [2][3][4][5] However, the mechanism by which IL-24 induces its selective apoptosis is complicated, depending on the cell type studied. Previous studies have demonstrated that IL-24 can induce apoptosis at multiple levels by activating caspase cascade and upregulating P53, Bax, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and growth arrest and DNA damage protein family genes.…”

Section: Introductionmentioning

confidence: 99%

The antitumor activity of TRAIL and IL-24 with replicating oncolytic adenovirus in colorectal cancer

Zhao

Dong

et al. 2006

Cancer Gene Ther

View full text Add to dashboard Cite

Melanoma differentiation associated gene-7 (Mda-7)/IL-24 was previously cloned into ZD55 (an adenovirus with E1B55 deleted) to form ZD55-IL-24, which had much better antitumor effect than Ad-IL-24. According to its good antitumor properties, ZD55-IL-24 has been used in preclinical studies. But ZD55-IL-24 alone still could not completely eradicate established tumors in all nude mice. It was reported that IL-24 could induce and enhance the activity of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (a member of tumor necrosis factor (TNF) superfamily). Accordingly, the combined use of ZD55-IL-24 and ZD55-TRAIL was carried out in this study. Treatment with both ZD55-IL-24 and ZD55-TRAIL could induce more significant apoptosis in cancer cells in vitro compared with ZD55-IL-24 or ZD55-TRAIL alone. The combination of the two replicative adenoviruses had better antitumor activity in vivo than that of single oncolytic adenovirus and led to complete eradication of xenograft tumors in all treated mice. Upregulation of TRAIL was observed in tumor cells infected with ZD55-IL-24 and studies of the apoptotic cascade regulators indicate that ZD55-IL-24 could further enhance the activation of apoptosis through the TNF family of death receptors. We demonstrated for the first time the potential therapeutic effect of combined ZD55-IL-24 with ZD55-TRAIL for the targeted therapy of cancer.

show abstract

Tumor-suppressive effects by adenovirus-mediated mda-7 gene transfer in non-small cell lung cancer cell in vitro

Cited by 147 publications

References 12 publications

Combinatorial synergy induced by adenoviral-mediated mda-7 and Herceptin in Her-2+ breast cancer cells

Combinatorial synergy induced by adenoviral-mediated mda-7 and Herceptin in Her-2+ breast cancer cells

Down-regulated melanoma differentiation associated gene (mda-7) expression in human melanomas

The antitumor activity of TRAIL and IL-24 with replicating oncolytic adenovirus in colorectal cancer

Contact Info

Product

Resources

About