TGF-β1 Triggers Oxidative Modifications and Enhances Apoptosis in Hit Cells Through Accumulation of Reactive Oxygen Species by Suppression of Catalase and Glutathione Peroxidase

Islam, Kazi Nazrul; Kayanoki, Yoshiro; Kaneto, Hideaki; Suzuki, Keiichiro; Asahi, Michio; Fujii, Junichi; Taniguchi, Naoyuki

doi:10.1016/s0891-5849(96)00493-5

Cited by 100 publications

(49 citation statements)

References 41 publications

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“…Therefore, more efficient conversion of superoxide into hydrogen peroxide, together with decreased removal of the latter, would result in accumulation of hydrogen peroxide within the tumour cells. Hydrogen peroxide has been implicated in causing genetic damage [24], while superoxide mediates apoptosis [25,26]. The high levels of Mn SOD with decreased catalase may create an anti-apoptotic intracellular environment which is especially susceptible to increased frequency of mutations, a situation likely to lead to cell transformation and cancer.…”

Section: Discussionmentioning

confidence: 99%

Disturbance of systemic antioxidant profile in nonsmall cell lung carcinoma

Chan‐Yeung²,

Ho³

et al. 2006

Eur Respir J

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The present study aimed to determine the alterations of antioxidant activities in erythrocytes from patients with nonsmall cell lung carcinoma (NSCLC).A comparative study of the systemic antioxidant activities in red blood cell lysate from subjects with NSCLC and healthy control subjects was conducted. The antioxidants catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx) were measured using chemical kinetic reactions under spectrophotometry.In total, 189 cases of mostly advanced-stage IIIB or stage IV NSCLC and 202 healthy controls were studied. In subjects with lung cancer, there was similar catalase activity, lower SOD activity (median (interquartile range) 13.4 (9.0-27.2) versus 48. ) compared with controls. The antioxidant activities in lung cancer subjects were not associated with age, sex, smoking status, or tumour cell types. However, more advanced disease (stage IV compared with stage IIIB) was associated with lower SOD activity. Using multivariable analysis, the presence of lung cancer independently predicted SOD and GPx activities.In conclusion, nonsmall cell lung carcinoma in Chinese subjects is associated with alterations in systemic antioxidant activities, which may play an important role in carcinogenesis.

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Section: Discussionmentioning

confidence: 99%

Disturbance of systemic antioxidant profile in nonsmall cell lung carcinoma

Chan‐Yeung²,

Ho³

et al. 2006

Eur Respir J

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“…However, the signaling pathways that specifically mediate TGF-␤-stimulated ECM protein production have not been well elucidated. Interestingly, it has been reported that TGF-␤ stimulates ROS production while ROS mediate various TGF-␤ effects, such as growth inhibition/apoptosis, production of IL-6 and macrophage colony-stimulating factor, and expression of early growth response-1 (9,17,19,21,29). Whether ROS is also involved in TGF-␤-stimulated collagen production has been less well studied.…”

Section: Discussionmentioning

confidence: 99%

Glutathione regulates transforming growth factor-β-stimulated collagen production in fibroblasts

Liu¹,

Liu²,

Forman³

et al. 2004

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…On the other hand, GPx-1 also increases tumorigenesis in transformed cells by limiting apoptotic mechanisms (14,15). It has been reported that TGF-β can suppress catalase and GPx-1 mRNA expression and reduce their antioxidative activities in chronic pancreatitis and rat hepatocytes (16,17). However, whether there is a regulatory interaction between TGF-β and GPx-1 in colorectal cancer cells remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Transforming growth factor-β1 induces glutathione peroxidase-1 and protects from H2O2-induced cell death in colon cancer cells via the Smad2/ERK1/2/HIF-1α pathway

et al. 2012

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Abstract.Recent studies have shown that transforming growth factor-β1 (TGF-β1) signaling plays important roles in the redox system in benign and malignant cells. Whether TGF-β mediates an antioxidative damage response in colorectal cancer cells is largely unknown. Herein, using the human colorectal cancer cell lines we found that TGF-β1 induced glutathione peroxidase-1 (GPx-1) expression and enzyme activity, and that the upregulation of GPx-1 by TGF-β1 could protect colorectal cell lines from H 2 O 2 -induced oxidation damage. Further, we used loss-and gain-function approaches to elucidate the underlying mechanism and found that TGF-β1 induced GPx-1 through activation of the TGF-β receptor type I (TGF-βRI)/ Smad2/extracellular-signal-regulated kinase 1/2 (ERK1/2)/ hypoxia-inducible factor-1α (HIF-1α) signaling pathway. This cascade could be blocked by the TGF-βRI inhibitor or ERK1/2 inhibitor. Taken together, our data demonstrated that TGF-β1 induced GPx-1 expression and enzymatic activity via the TGF-βRI/Smad2/ERK1/2/HIF-1α signaling pathway, suggesting a novel antioxidative protective function of TGF-β1 in colorectal cancer cells. IntroductionTransforming growth factor-β (TGF-β) is a multifunctional cytokine and plays very important roles in development, differentiation and in maintaining homeostasis in almost all cell types and tissues (1). TGF-β functions via transmembrane serine/threonine kinase receptors, the type I and type II receptors (TGF-βRI and TGF-βRII) (2) and intracellular Smad transcriptional regulators (3). Increasing evidence has indicated that TGF-β is involved in the redox system in benign and tumor cells, in terms of that TGF-β can induce production of reactive oxygen species (ROS) which stimulates proliferation, invasion, migration and angiogenesis and evade apoptosis in cancer cells (4). TGF-β1 can stimulate a rapid increase in ROS generation to induce kidney myofibroblast activation and matrix synthesis (5). In renal tubular epithelial cells, TGF-β1 induces cellular ROS and mediates the epithelial-mesenchymal transition (EMT). All these effects can be abrogated by antioxidants (6). Low levels of ROS play a very important role in keeping normal cell proliferation by regulating cellular signaling. A great body of evidence indicates that production of ROS is increased in cancer cells and elevated ROS may facilitate tumor cell growth (7). However, a higher level of ROS may act reversely to induce an apoptotic response of tumor cells. Moderate ROS levels provide tumor cells with the advantage to maintain survival. Glutathione peroxidases (GPxs) are of the most important antioxidative enzyme families which can modulate cellular ROS levels to keep the redox balance in tumor cells.GPx-1 is the first identified selenoprotein and is expressed in most cells (8-10). GPx-1 is classified as an antioxidant enzyme and exerts its role to prevent the initiation of cancer by ROS-mediated DNA damage. Previous studies have suggested that GPx-1 is altered in several types of cancer cells (11,12) and overexpres...

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TGF-β1 Triggers Oxidative Modifications and Enhances Apoptosis in Hit Cells Through Accumulation of Reactive Oxygen Species by Suppression of Catalase and Glutathione Peroxidase

Cited by 100 publications

References 41 publications

Disturbance of systemic antioxidant profile in nonsmall cell lung carcinoma

Disturbance of systemic antioxidant profile in nonsmall cell lung carcinoma

Glutathione regulates transforming growth factor-β-stimulated collagen production in fibroblasts

Transforming growth factor-β1 induces glutathione peroxidase-1 and protects from H2O2-induced cell death in colon cancer cells via the Smad2/ERK1/2/HIF-1α pathway

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