Thymoquinone induces oxidative stress-mediated apoptosis through downregulation of Jak2/STAT3 signaling pathway in human melanoma cells

Raut, Pawan Kumar; Lee, Hui Seong; Joo, Sang Hoon; Chun, Kyung‐Soo

doi:10.1016/j.fct.2021.112604

Cited by 24 publications

(22 citation statements)

References 54 publications

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“…Therefore, any treatment counteracting STAT3 hyperactivation has been considered a potential strategy to treat different tumors. Over the past years, various studies have also demonstrated the relation between the anti-proliferative and pro-apoptotic effects of some EOs and their anti-STAT3 activity [ 29 , 30 , 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

Pinus mugo Essential Oil Impairs STAT3 Activation through Oxidative Stress and Induces Apoptosis in Prostate Cancer Cells

et al. 2022

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Essential oils (EOs) and their components have been reported to possess anticancer properties and to increase the sensitivity of cancer cells to chemotherapy. The aim of this work was to select EOs able to downregulate STAT3 signaling using Western blot and RT-PCR analyses. The molecular mechanism of anti-STAT3 activity was evaluated through spectrophotometric and fluorometric analyses, and the biological effect of STAT3 inhibition was analyzed by flow cytometry and wound healing assay. Herein, Pinus mugo EO (PMEO) is identified as an inhibitor of constitutive STAT3 phosphorylation in human prostate cancer cells, DU145. The down-modulation of the STAT3 signaling cascade decreased the expression of anti-proliferative as well as anti-apoptotic genes and proteins, leading to the inhibition of cell migration and apoptotic cell death. PMEO treatment induced a rapid drop in glutathione (GSH) levels and an increase in reactive oxygen species (ROS) concentration, resulting in mild oxidative stress. Pretreatment of cells with N-acetyl-cysteine (NAC), a cell-permeable ROS scavenger, reverted the inhibitory action of PMEO on STAT3 phosphorylation. Moreover, combination therapy revealed that PMEO treatment displayed synergism with cisplatin in inducing the cytotoxic effect. Overall, our data highlight the importance of STAT3 signaling in PMEO cytotoxic activity, as well as the possibility of developing adjuvant therapy or sensitizing cancer cells to conventional chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Pinus mugo Essential Oil Impairs STAT3 Activation through Oxidative Stress and Induces Apoptosis in Prostate Cancer Cells

et al. 2022

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“…In a septic mouse model, blocking the JAK2/STAT3 signaling pathway significantly reduced the levels of HMGB1 and key cytokines and alleviated multi-organ injury ( Hui et al, 2009 ; Xin et al, 2020 ). In addition, the JAK2/STAT3 pathway affects cell apoptosis by altering the levels of Bcl-2 and Bax and influencing oxidative stress ( Li et al, 2017 ; Raut et al, 2021 ). Therefore, we hypothesized that IMD could reduce oxidative stress and apoptosis through the JAK2/STAT3 pathway and protected against VILI.…”

Section: Discussionmentioning

confidence: 99%

Intermedin Reduces Oxidative Stress and Apoptosis in Ventilator-Induced Lung Injury via JAK2/STAT3

Fan

Yang

et al. 2022

Front. Pharmacol.

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Mechanical ventilation is an effective treatment for acute respiratory distress syndrome (ARDS), which can improve the prognosis of ARDS to a certain extent. However, it may further aggravate lung tissue injury, which is defined as ventilator-induced lung injury (VILI). Intermedin (IMD) belongs to the calcitonin gene-related peptide (CPRP) superfamily. Our previous studies have found that IMD reduces the expression proinflammatory cytokines, down-regulates nuclear translocation and improves the integrity of endothelial barrier in ARDS. However, the effect of IMD on VILI has not been clarified. Oxidative stress imbalance and apoptosis are the main pathophysiological characteristics of VILI. In the current study, we used C57B6/J mice and human pulmonary microvascular endothelial cells (HPMECs) to establish a VILI model to analyze the effects of IMD on VILI and explore its potential mechanism. We found that IMD alleviated lung injury and inflammatory response in VILI, mainly in reducing ROS levels, upregulating SOD content, downregulating MDA content, reducing the expression of Bax and caspase-3, and increasing the expression of Bcl-2. In addition, we also found that IMD played its anti-oxidative stress and anti-apoptotic effects via JAK2/STAT3 signaling. Our study may provide some help for the prevention and treatment of VILI.

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“…TQ has an effective role in the reduction of endothelial cell migration, tube formation, and suppression of tumor angiogenesis. TQ noticeably reduces the phosphorylation of EGFR at tyrosine-1173 residues and JAK2 in vitro in HCT 116 human colon cancer cells and downregulates the Jak2/STAT3 signaling pathway in human melanoma cells and HL60 leukemia cells [ 232 , 233 , 234 ]. TQ causes G2/M cell cycle arrest and stirred apoptosis, and it significantly lowers the nuclear expression of NF-κB.…”

Section: Plant-derived Natural Products With Potential Anticancer Eff...mentioning

confidence: 99%

Plants as a Source of Anticancer Agents: From Bench to Bedside

et al. 2022

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Cancer is the second leading cause of death after cardiovascular diseases. Conventional anticancer therapies are associated with lack of selectivity and serious side effects. Cancer hallmarks are biological capabilities acquired by cancer cells during neoplastic transformation. Targeting multiple cancer hallmarks is a promising strategy to treat cancer. The diversity in chemical structure and the relatively low toxicity make plant-derived natural products a promising source for the development of new and more effective anticancer therapies that have the capacity to target multiple hallmarks in cancer. In this review, we discussed the anticancer activities of ten natural products extracted from plants. The majority of these products inhibit cancer by targeting multiple cancer hallmarks, and many of these chemicals have reached clinical applications. Studies discussed in this review provide a solid ground for researchers and physicians to design more effective combination anticancer therapies using plant-derived natural products.

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Thymoquinone induces oxidative stress-mediated apoptosis through downregulation of Jak2/STAT3 signaling pathway in human melanoma cells

Cited by 24 publications

References 54 publications

Pinus mugo Essential Oil Impairs STAT3 Activation through Oxidative Stress and Induces Apoptosis in Prostate Cancer Cells

Pinus mugo Essential Oil Impairs STAT3 Activation through Oxidative Stress and Induces Apoptosis in Prostate Cancer Cells

Intermedin Reduces Oxidative Stress and Apoptosis in Ventilator-Induced Lung Injury via JAK2/STAT3

Plants as a Source of Anticancer Agents: From Bench to Bedside

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