Regulation by IFN-&amp;#945;/IFN-&amp;#947; Co-Formulation (HerberPAG&lt;sup&gt;®&lt;/sup&gt;) of Genes Involved in Interferon-STAT-Pathways and Apoptosis in U87MG

Bello, Claudia; Vázquez-Blomquist, Dania; Miranda, Jamilet; Garcia, Yanelda; Novoa, Lidia I; Palenzuela, Daniel; Bello, Iraldo

doi:10.2174/1568026613666131204125725

Cited by 11 publications

(6 citation statements)

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“…IFN-β inhibits HepG2 cell viability via phosphorylation of STAT2 (24). Also, an IFN-α/IFN-γ co-formulation is involved in the IFN-STAT-pathway and apoptosis in U87MG cells (25). Some of the stimulated apoptosis may be explained by the upregulation of mitochondria respiratory complexes and ROS production (26,27).…”

Section: Introductionmentioning

confidence: 99%

The STAT-ROS cycle extends IFN‑induced cancer cell apoptosis

et al. 2017

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In mammals, the signal transducer and activator of transcription (STAT) protein processes mitochondria importation targets and mitochondria respiratory complexes, and triggers reactive oxygen species (ROS) generation, which conversely rapidly initiates the activation of STAT. Interferon (IFN) administration increases cancer cell apoptosis via STAT activation and ROS accumulation. However, the existence of a STAT-ROS cycle and how it affects IFN-induced cancer cellular apoptosis are unclear. In the present study, we used MCF7 breast cancer cells and confirmed that a combination of IFN-α/β/γ incubation induced STAT1/3 phosphorylation and mitochondria importation, which increased mitochondria respiratory complexes, the cellular oxygen consumption rate (OCR), and ROS production, followed by cellular apoptosis. We also found that STAT1/3 overexpression induced mitochondria respiratory complexes and ROS production. Additionally, ROS induced by H 2 O 2 induced phosphorylation of STAT1/3 and promoted mitochondria importation. STAT1/3 deletion suppressed H 2 O 2-induced acute cellular OCR, increasing the ROS level and indicating that STAT1/3 is necessary for ROS-induced mitochondria OCR and further ROS production, suggesting the existence of a STAT-ROS cycle. We next found that IFN induced mitochondria respiratory complexes followed by induction of OCR, ROS, and apoptosis, which were partially blocked by STAT1/3 deletion. Additionally, the suppression of ROS inhibited IFN-induced STAT1/3 activation. Finally, we discovered that this cycle exists also in A431 and HeLa cancer cells. These results indicate that a STAT-ROS cycle extends IFN-induced cellular apoptosis.

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Section: Introductionmentioning

confidence: 99%

The STAT-ROS cycle extends IFN‑induced cancer cell apoptosis

et al. 2017

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“…Both IFNs have anti-angiogenic activity and significantly suppress the expression of the CXCR-4 gene, which in turn can decrease the vascularity surrounding non-melanoma skin cancer and affect the migration induced by SDF-1 and also the migration of CXCR-4 positive cells, as has been demonstrated in squamous cell carcinomas of the head and neck for IFN-. All these properties of IFN, among others, probably contribute to increase the antitumor activity of this new formulation of IFN 20,35 .…”

Section: Discussionmentioning

confidence: 99%

Synergistic effect of combined IFN-alpha2b and IFN-gamma treatment for periocular basal cell carcinoma

Negrín-Caceres¹,

Cabrera-Romero²,

Cárdenas-Monzón³

et al. 2019

RMOE

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Purpose: To assess the results of the application of perilesional HerberPAG® on periocular basal cell carcinoma. Methods: An experimental investigation was carried out on a group of 7 patients who received the same treatment regimen with Heber-PAG® 10.5 × 10 6 IU 3 times a week for 3 consecutive weeks. Demographic variables were evaluated as well as duration, initial lesion size, clinical subtype, histological subtype, clinical response, objective response and adverse events. Results: The average time of lesion duration was 7.0 ± 1.6 months, with a large diameter mean of 17.4 ± 2.3 mm. The clinical nodular-ulcerative subtype was present on 42.9% of the subjects and the solid and superficial histological subtypes were present with an equal proportion of 42.9%. Conclusions: The use of HerberPAG® was an effective and safe alternative to conservative treatment in subjects with periocular basal cell carcinoma when other therapies are not available.

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“…The proteins, enzymes and metabolites mediating the antiviral effect (2-5 OAS, β-2 microglobulin, Neopterin) of IFNs are synergistically stimulated by HeberFERON 28,29 . The main intracellular signaling factor common to both IFNs, STAT-1 7 has also been synergistically stimulated and has been shown to be a target of SARS-CoV antagonism on the IFN system 12 .…”

Section: Heberferon®mentioning

confidence: 99%

Evaluation of the Effect and Safety of HeberFERON vs Heberon Alpha in Patients Infected with Corona Virus SARS-CoV-2 (Study ESPERANZA/HOPE): Study Protocol for a Randomized Controlled Trial.

Bello-Rivero¹,

Hernández-Bernal²,

Nodarse-Cuní³

et al. 2020

Preprint

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Background: As the outbreak of COVID-19 has accelerated, an urgent need for finding strategies to combat the virus is growing. Results from in vitro studies suggest that a combination of IFN type I and Type II may be effective against SARS-CoV. The aim of this study is to investigate the efficacy of treatment with a recombinant IFN alpha 2b and gamma, provided with standard protocol (Kaletra (lopinavir-ritonavir 200/50 mg; 200/100 mg every 12 hour for 30 days; Chloroquine (250 mg) every 12 hours for 10 days) for COVID-19 patients, compared to standard protocol (IFN alpha 2b/Kaletra/Chloroquine) for COVID-19 hospitalized patients, positive diagnosed for SARS-Cov-2. Methods: Hospitalized adult patients with qPCR confirmed SARS-Cov-2 will be enrolled in this open-labeled, single center, prospective, randomized and controlled clinical trial. One hundred and twenty eligible patients with confirmed SARS-CoV-2 positivity by qPCR amplification in oropharyngeal/nasopharyngeal swab samples will be enrolled at “Luis Diaz Soto” Hospital, Havana, Cuba. The primary outcomes are the time to 2019-nCoV RNA negativity in patients and the time until progression to severe COVID-19. Discussion: This will be the first randomized controlled trial of a potential treatment for SARC-Cov-2 using the combinations of IFNs. Trial registration: The study is sponsored by Center for Genetic and Biotechnology and Ministry of Health of Cuba and was duly registered April 2020 at http://registroclinico.sld.cu/en/trials/RPCEC00000307-En. Enrolment for this study began in April 11, 2020, and has enrolled one hundred patients as of May-26-2020

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Regulation by IFN-α/IFN-γ Co-Formulation (HerberPAG<sup>®</sup>) of Genes Involved in Interferon-STAT-Pathways and Apoptosis in U87MG

Cited by 11 publications

References 0 publications

The STAT-ROS cycle extends IFN‑induced cancer cell apoptosis

The STAT-ROS cycle extends IFN‑induced cancer cell apoptosis

Synergistic effect of combined IFN-alpha2b and IFN-gamma treatment for periocular basal cell carcinoma

Evaluation of the Effect and Safety of HeberFERON vs Heberon Alpha in Patients Infected with Corona Virus SARS-CoV-2 (Study ESPERANZA/HOPE): Study Protocol for a Randomized Controlled Trial.

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