Reactive oxygen species and PI3K/Akt signaling in cancer

Jin, Seo Yeon; Lee, Hye Sun; Kim, Eun Kyoung; Ha, Jung Min; Kim, Young Whan; Bae, Sun-Sik

doi:10.1016/j.freeradbiomed.2014.10.773

Cited by 21 publications

(10 citation statements)

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“… 26 ROS is a series of derivatives that are generated during the metabolic process by aerobic cells, and participate in and influence a range of cellular signaling pathways, including activating PI3K/AKT/mTOR signaling pathway. 41 …”

Section: Discussionmentioning

confidence: 99%

The inhibitory mechanism of <em>Cordyceps sinensis</em> on cigarette smoke extract-induced senescence in human bronchial epithelial cells

Liu¹,

Wu²,

Li³

et al. 2016

COPD

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ObjectivesCellular senescence is a state of irreversible growth arrest induced either by telomere shortening (replicative senescence) or stress. The bronchial epithelial cell is often injured by inhaled toxic substances, such as cigarette smoke. In the present study, we investigated whether exposure to cigarette smoke extract (CSE) induces senescence of bronchial epithelial cells; and Cordyceps sinensis mechanism of inhibition of CSE-induced cellular senescence.MethodsHuman bronchial epithelial cells (16HBE cells) cultured in vitro were treated with CSE and/or C. sinensis. p16, p21, and senescence-associated-galactosidase activity were used to detect cellular senescence with immunofluorescence, quantitative polymerase chain reaction, and Western blotting. Reactive oxygen species (ROS), PI3K/AKT/mTOR and their phosphorylated proteins were examined to testify the activation of signaling pathway by ROS fluorescent staining and Western blotting. Then, inhibitors of ROS and PI3K were used to further confirm the function of this pathway.ResultsCellular senescence was upregulated by CSE treatment, and C. sinensis can decrease CSE-induced cellular senescence. Activation of ROS/PI3K/AKT/mTOR signaling pathway was enhanced by CSE treatment, and decreased when C. sinensis was added. Blocking ROS/PI3K/AKT/mTOR signaling pathway can attenuate CSE-induced cellular senescence.ConclusionCSE can induce cellular senescence in human bronchial epithelial cells, and ROS/PI3K/AKT/mTOR signaling pathway may play an important role in this process. C. sinensis can inhibit the CSE-induced senescence.

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Section: Discussionmentioning

confidence: 99%

The inhibitory mechanism of <em>Cordyceps sinensis</em> on cigarette smoke extract-induced senescence in human bronchial epithelial cells

Liu¹,

Wu²,

Li³

et al. 2016

COPD

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“…Superoxide, hydrogen peroxide, and hydroxyl radicals are the most-well studied ROS in cancer cells [14]. A previous study has shown that ROS are capable of causing extensive damage to DNA, proteins, and lipids, and thus it is believed that ROS is tumorigenic by increasing genomic instability [15].…”

Section: Introductionmentioning

confidence: 99%

Protodioscin Induces Apoptosis Through ROS-Mediated Endoplasmic Reticulum Stress via the JNK/p38 Activation Pathways in Human Cervical Cancer Cells

Lin

Lee

Chen

et al. 2018

Cell Physiol Biochem

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Background/Aims: Protodioscin (PD) is a steroidal saponin with anti-cancer effects on a number of cancer cells, but the anti-tumor effects and mechanism of action of PD on human cervical cancer cells is unclear. Methods: We determined cell viability using the MTT assay. Cell death, mitochondrial membrane potential (MMP), intracellular reactive oxygen species (ROS) generation, and endoplasmic reticulum (ER) stress were measured on a flow cytometry. Caspase activation, ER stress, and MMP-dependent apoptosis proteins in cervical cancer cells in response to PD were determined by Western blot analysis. The ability of ATF4 binding to ChIP promoter was measured using the ChIP assay. Results: We demonstrated that PD inhibits cell viability, causes a loss of mitochondrial function, and induces apoptosis, as evidenced by up-regulation of caspase-8, -3, -9, -PARP, and Bax activation, and down-regulation of Bcl-2 expression. PD was shown to induce ROS and the ER stress pathway, including GRP78, p-eIF-2α, ATF4, and CHOP. Pre-treatment with NAC, a ROS production inhibitor, significantly reduced ER stress and apoptosis-related proteins induced by PD. Transfection of GRP78/CHOP-siRNA effectively inhibited PD-induced ER stress-dependent apoptosis. Moreover, treatment with PD significantly increased p38 and JNK activation. Co-administration of a JNK inhibitor (SP600125) or p38 inhibitor (SB203580) abolished cell death and ER stress effects during PD treatment. In addition, PD induced the expression of nuclear ATF4 and CHOP, as well as the binding ability of ATF4 to the CHOP promoter. Conclusion: Our results suggest that PD is a promising therapeutic agent for the treatment of human cervical cancer.

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“…It is worth considering that ROS production was responsible for the inhibition of the PI3K/Akt pathway by deoxyschizandrin in human ovarian cancer cells. Jin et al have suggested that ROS generation is closely related with the Akt signalling pathway [ 41 ]. The major functions of Akt are promotion of growth factor-mediated cell proliferation through phosphorylation of many physiological substrates and inhibition of apoptosis through the inactivation of pro-apoptotic proteins [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Deoxyschizandrin, Isolated from Schisandra Berries, Induces Cell Cycle Arrest in Ovarian Cancer Cells and Inhibits the Protumoural Activation of Tumour-Associated Macrophages

et al. 2018

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Deoxyschizandrin, a major lignan of Schisandra berries, has been demonstrated to have various biological activities such as antioxidant, hepatoprotective, and antidiabetic effects. However, the anti-cancer effects of deoxyschizandrin are poorly characterized. In the present study, we investigated the anti-cancer effect of deoxyschizandrin on human ovarian cancer cell lines and tumour-associated macrophages (TAMs). Deoxyschizandrin induced G0/G1 phase cell cycle arrest and inhibited cyclin E expression in human ovarian cancer cells. Overexpression of cyclin E significantly reversed the deoxyschizandrin-induced cell growth inhibition. Interestingly, increased production of reactive oxygen species and decreased activation of Akt were observed in A2780 cells treated with deoxyschizandrin, and the antioxidant compromised the deoxyschizandrin-induced cell growth inhibition and Akt inactivation. Moreover, deoxyschizandrin-induced cell growth inhibition was markedly suppressed by Akt overexpression. In addition, deoxyschizandrin was found to inhibit the expression of the M2 phenotype markers CD163 and CD209 in TAMs, macrophages stimulated by the ovarian cancer cells. Moreover, expression and production of the tumour-promoting factors MMP-9, RANTES, and VEGF, which are highly enhanced in TAMs, was significantly suppressed by deoxyschizandrin treatment. Taken together, these data suggest that deoxyschizandrin exerts anti-cancer effects by inducing G0/G1 cell cycle arrest in ovarian cancer cells and reducing the protumoural phenotype of TAMs.

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Reactive oxygen species and PI3K/Akt signaling in cancer

Cited by 21 publications

References 0 publications

The inhibitory mechanism of <em>Cordyceps sinensis</em> on cigarette smoke extract-induced senescence in human bronchial epithelial cells

The inhibitory mechanism of <em>Cordyceps sinensis</em> on cigarette smoke extract-induced senescence in human bronchial epithelial cells

Protodioscin Induces Apoptosis Through ROS-Mediated Endoplasmic Reticulum Stress via the JNK/p38 Activation Pathways in Human Cervical Cancer Cells

Deoxyschizandrin, Isolated from Schisandra Berries, Induces Cell Cycle Arrest in Ovarian Cancer Cells and Inhibits the Protumoural Activation of Tumour-Associated Macrophages

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