Inhibitory effects of interferon‐β on hepatocellular carcinoma <scp>H</scp>ep<scp>G</scp>2 via <scp>A</scp>kt/<scp>STAT</scp> phosphorylation

Ethiraj, Purushoth; Veerappan, Karpagam; Samuel, Shila; Sundaresan, Sivapatham

doi:10.1111/fcp.12115

Cited by 3 publications

(2 citation statements)

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“…It is already known that IFN-γ induces cellular apoptosis mediated by STAT1 activation (23). 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).…”

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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“…While ADR is one of the most effective chemotherapeutic drugs, its incidence of toxicity compromises its therapeutic index. It has some side effects on non-cancerous tissue such as liver [23]. ADR seems to accumulate mostly in the liver, most likely due to the organ's role in drug metabolism [20].…”

Section: Discussionmentioning

confidence: 99%

Counteraction of Apoptotic and Inflammatory Effects of Adriamycin in the Liver Cell Culture by Clinopitolite

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et al. 2015

Biol Trace Elem Res

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Growing evidence has been reported on adriamycin (ADR) hepatotoxicity in literature. Hepatotoxicity caused by the use of drugs has a serious undesirable effect in the cure of cancer patients that needs to be eliminated. The exact mechanism of ADR on non-cancerous tissue still remains to be a mystery. The zeolite (clinoptilolite) minerals form a complex group of aluminosilicates that often occur as accessory minerals in intermediate and basic rocks. In light of this information, we investigated the possible anti-inflammatory and anti-apoptotic effects of clinoptilolite in ADR that is inducing the toxicity in primary liver cell culture. Primary liver cell culture from rat was used in the study. We had three experiment groups including the following: (1) cells treated only with 50 μM ADR for 24 h, (2) cells treated with the 50 μM ADR for 24 h and then treated with 10(-4) M zeolite for 1 h, and (3) cells were incubated with 50 μM ADR for 24 h and then incubated with 10(-4) M zeolite for 24 h to test its long-term effects. After that, western blotting was performed in order to evaluate protein expression levels of several inflammation markers including IL-1β, tumor necrosis factor (TNF)-α, and nuclear factor kappa B (NF-κB), and immunohistochemistry was carried out to detect apoptosis in liver cell culture. Also, TdT-dUTP Terminal Nick-End Labeling (TUNEL) method was used for detecting apoptosis. We found elevated levels of inflammatory protein and apoptotic markers in ADR-administered cells (p < 0.05). Inflammatory and apoptotic markers decreased significantly after treated with zeolite (p < 0.05). The present study was pointed out that ADR causes hepatotoxicity via apoptosis and/or inflammation processes resulting from initiator NF-κB and TNF which causes proinflammatory mediators such as IL-1β. Elevation of inflammation might give rise to trigger apoptosis. Clinoptilolite counteracted the apoptosis and inflammation induced by ADR arising from the decrease in NF-κB, TNF-α, and IL-1β protein levels.

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