Type I consensus interferon (CIFN) gene transfer into human melanoma cells up-regulates p53 and enhances cisplatin-induced apoptosis: implications for new therapeutic strategies with IFN-alpha

Mecchia, Monica; Matarrese, Paola; Malorni, Walter; D’Agostino, Giuseppina; Sestili, Paola; Santini, Stefano M.; Gauzzi, Maria Cristina; Venditti, Massimo; Mazzocchi, Arabella; Parmiani, Giorgio; Belardelli, Filippo; Ferrantini, Maria

doi:10.1038/sj.gt.3301059

Cited by 22 publications

(24 citation statements)

References 41 publications

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“…20 We have recently shown that the retroviral transduction of human consensus IFN (CIFN) coding sequence into two human melanoma cell lines resulted in a strong augmentation of cisplatin-induced apoptosis, associated with an IFN-dependent increase in p53 expression. 22 Similar effects, although less marked, were also observed after cultivation of parental melanoma cells in the presence of exogenous IFN. Cisplatin administration to nude mice bearing IFN-producing tumors resulted in complete tumor regression, whereas only partial tumor inhibition was observed after cisplatin treatment of mice with control tumors.…”

supporting

confidence: 57%

“…22 The 1B6 clone was isolated from the M10538 cell line, established from a primary skin melanoma lesion, 27 whereas the 8863 cell line was derived from a metastatic melanoma. 28 The HLA haplotype of the two patients was previously identified.…”

Section: Cell Linesmentioning

confidence: 99%

“…30 Both LXSN and LCIFNSN recombinant retroviruses were obtained following standard trans-infection procedures in GPϩE86 31 and GpϩenvAm12 32,33 packaging cells as previously reported. 22 LXSN and LCIFNSN retroviruses were used for infection of 1B6 and 8863 melanoma cells, as previously described. 22 After selection into G418-containing medium, control transduced cells (LXSN) or cells producing ϳ1000 IU/ml IFN (LCIFNSN) were isolated from both 1B6 and 8863 cell lines.…”

Section: Recombinant Retrovirus Production and Infection Of Melanoma mentioning

confidence: 99%

“…Cisplatin administration to nude mice bearing IFN-producing tumors resulted in complete tumor regression, whereas only partial tumor inhibition was observed after cisplatin treatment of mice with control tumors. 22 In the present work we partially address the mechanisms underlying the IFN-induced modulation of melanoma cell susceptibility to cisPt, pointing to the mitochondrial activity and related redox homeostasis as "supervisors" of cell susceptibility to apoptotic triggering.…”

mentioning

confidence: 99%

“…18 In recent years cytokine gene transfer into tumor cells has received particular attention as a potentially useful approach for cancer therapy. 19 Studies by our group, as well as by other groups, have for instance shown that type I interferon (IFN) gene transfer into different tumor cell lines resulted in 1) a marked loss of tumorigenicity, 20 2) a down-regulation of oncogene expression and induction of tumor suppressor genes contributing to the anti-proliferative activity, [21][22][23][24] and 3) an increase in MHC class I expression that can enhance immune recognition. 20,25,26 Moreover, it has been reported that IFN-␣ gene transfer sensitizes human tumor cells to apoptosis induced by cytotoxic agents, and that a better therapeutic effect could be achieved when the treatment of tumor-bearing mice with IFN-expressing cells was combined with chemotherapy.…”

mentioning

confidence: 99%

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Type I Interferon Gene Transfer Sensitizes Melanoma Cells to Apoptosis via a Target Activity on Mitochondrial Function

Matarrese

Biase

Santodonato

et al. 2002

The American Journal of Pathology

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Our previous article reported that retroviral transduction of human type I consensus interferon-coding sequence into two human melanoma cells increased their susceptibility to cisplatin-induced apoptosis. Importantly, primary melanoma cells were significantly more sensitive to cisplatin-induced apoptosis with respect to metastatic melanoma cells. The aim of this study was to elucidate the subcellular mechanisms involved in this interferon-induced apoptotic proneness. Our results indicate that 1) cisplatin-induced apoptosis can be referred to as the type II apoptosis, ie, to the mitochondrially driven cascade; 2) treatment of interferon-producing melanoma cells with other type II apoptotic stimuli, such as radiation or staurosporine, also resulted in massive apoptosis, whereas type I stimuli, ie, anti-Fas, were ineffective; 3) interferon sensitization involved the caspase cascade in primary melanoma cells and the alternative pathway represented by cathepsin-mediated apoptosis in metastatic melanoma cells; 4) interferon production sensitizes cells to apoptosis by inducing, as the earliest event, mitochondrial membrane hyperpolarization. These results suggest that constitutive production of type I interferon by melanoma cells can act as an intracellular booster capable of increasing cell proneness to apoptosis by specifically modifying mitochondrial homeostasis and independently from the apoptotic cascade involved. (Am J Pathol 2002,

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supporting

confidence: 57%

Section: Cell Linesmentioning

confidence: 99%

Section: Recombinant Retrovirus Production and Infection Of Melanoma mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Type I Interferon Gene Transfer Sensitizes Melanoma Cells to Apoptosis via a Target Activity on Mitochondrial Function

Matarrese

Biase

Santodonato

et al. 2002

The American Journal of Pathology

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Role of IRF‐1 and caspase‐7 in IFN‐γ enhancement of Fas‐mediated apoptosis in ACHN renal cell carcinoma cells

Tomita

Bilim

Hara

et al. 2003

Intl Journal of Cancer

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Interferon‐α and antisense K‐ras RNA combination gene therapy against pancreatic cancer

Hatanaka¹,

Suzuki²,

Miura³

et al. 2004

The Journal of Gene Medicine

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Interferon alpha (IFN-alpha) is used worldwide for the treatment of a variety of cancers. For pancreatic cancer, recent clinical trials using IFN-alpha in combination with standard chemotherapeutic drugs showed some antitumor activity of the cytokine, but the effect was not significant enough to enlist pancreatic cancer as a clinically effective target of IFN-alpha. In general, an improved therapeutic effect and safety are expected for cytokine therapy when given in a gene therapy context, because the technology would allow increased local concentrations of this cytokine in the target sites. In this study, we first examined the antiproliferative effect of IFN-alpha gene transduction into pancreatic cancer cells. The expression of IFN-alpha effectively induced growth suppression and cell death in pancreatic cancer cells, an effect which appeared to be more prominent when compared with other types of cancers and normal cells. Another strategy we have been developing for pancreatic cancer targets its characteristic genetic aberration, K-ras point mutation, and we reported that the expression of antisense K-ras RNA significantly suppressed the growth of pancreatic cancer cells. When these two gene therapy strategies are combined, the expression of antisense K-ras RNA significantly enhanced IFN-alpha-induced cell death (1.3- to 3.5-fold), and suppressed subcutaneous growth of pancreatic cancer cells in mice. Because the 2',5'-oligoadenylate synthetase/RNase L pathway, which is regulated by IFN and induces apoptosis of cells, is activated by double-strand RNA, it is plausible that the double-strand RNA formed by antisense and endogenous K-ras RNA enhanced the antitumor activity of IFN-alpha. This study suggested that the combination of IFN-alpha and antisense K-ras RNA is a promising gene therapy strategy against pancreatic cancer.

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Type I consensus interferon (CIFN) gene transfer into human melanoma cells up-regulates p53 and enhances cisplatin-induced apoptosis: implications for new therapeutic strategies with IFN-alpha

Cited by 22 publications

References 41 publications

Type I Interferon Gene Transfer Sensitizes Melanoma Cells to Apoptosis via a Target Activity on Mitochondrial Function

Type I Interferon Gene Transfer Sensitizes Melanoma Cells to Apoptosis via a Target Activity on Mitochondrial Function

Role of IRF‐1 and caspase‐7 in IFN‐γ enhancement of Fas‐mediated apoptosis in ACHN renal cell carcinoma cells

Interferon‐α and antisense K‐ras RNA combination gene therapy against pancreatic cancer

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