Glycogen synthase kinase-3β regulates tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-induced apoptosis via the NF-κB pathway in hepatocellular carcinoma

Fu, Kai; Pan, Huazheng; Liu, Shihai; Lv, Jing; Wan, Zhaojun; Li, Jiao; Sun, Qing; Liang, Jun

doi:10.3892/ol.2015.3803

Cited by 4 publications

(4 citation statements)

References 38 publications

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“…However, we suggested the first in vitro evidence that miR-15a induced cell apoptosis by regulating GSK-3β. In fact, GSK-3β has been implicated in apoptosis under a variety of conditions, including DNA damage, endoplasmic reticulum stress, and hypoxia ( 22 ). It has been identified as a target of Akt, which plays a role in the regulation of apoptosis ( 23 ), and the activated GSK-3β activates downstream proapoptotic proteins (e.g., caspase 3 and Bax) ( 24,25 ).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-15a Inhibits Proliferation and Induces Apoptosis in CNE1 Nasopharyngeal Carcinoma Cells

Zhu

He²,

Cui³

et al. 2016

oncol res

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Nasopharyngeal carcinoma (NPC) is a highly metastatic cancer, frequently occurring in Southeast Asia and Southern China. Several microRNAs (miRNAs) have been shown to have an inhibitive effect on NPC, while the effect of miR-15a on NPC remains unclear. Thus, our study aimed to investigate the potential effect of miR-15a on NPC cell proliferation, apoptosis, and possible functional mechanism. Human NPC CNE1 cells were transfected with miR-15a mimics, miR-15a inhibitors, or a control. Afterward, cell viability and apoptosis were assayed by using CCK-8, BrdU assay, and flow cytometry. Moreover, Western blot was used to detect the expression changes of proliferation and apoptosis of related proteins. As a result, miR-15a overexpression significantly reduced cell proliferation (p < 0.01 or p < 0.001) and induced cell apoptosis (p < 0.001), while miR-15a suppression got the opposite result for cell proliferation and apoptosis. In addition, miR-15a overexpression upregulated the protein levels of p27, GSK-3β, Bax, procaspase 3, and active caspase 3, whereas miR-15a suppression downregulated these proteins. The protein level of p21 was not significantly regulated by miR-15a overexpression or suppression. These results indicated that miR-15a played a role for inhibition of proliferation and induction of apoptosis in CNE1 cells.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-15a Inhibits Proliferation and Induces Apoptosis in CNE1 Nasopharyngeal Carcinoma Cells

Zhu

He²,

Cui³

et al. 2016

oncol res

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“…As shown in Table 1, GSK3β sustains tumor cell survival in many cancer types by exploiting various pro-survival pathways mediated by nuclear factor (NF)κ-B [48,[52][53][54][55]63,78,94,95,98,107,128,129,151,153], Hh/Gli [43], mammalian target of rapamycin (mTOR) [97,140] and signal transducers and activators of transcription (STAT)3 [27,68]. Additionally, GSK3β helps tolerate apoptotic stimuli induced by the tumor necrosis factor-related apoptosis inducing ligand (TRAIL) receptor-dependent synthetic lethal system [36,57,61,71,74,83,107]. GSK3β can also perturb the p53-mediated tumor suppressor pathway [34,35,40,103,127,158] and Rb-mediated cell cycle regulatory machinery [29,62,109].…”

Section: Gsk3β and Tumor Cell Survival Evasion Of Apoptosis And Prolmentioning

confidence: 99%

“…To date, the tumor-promoting functions of deregulated GSK3β have been reported in 25 cancer types from various organs and tissues across the body ( Table 1 ) [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 ...…”

Section: Tumor-promoting Roles Of Gsk3β In Various Cancer Typesmentioning

confidence: 99%

Glycogen Synthase Kinase 3β in Cancer Biology and Treatment

Domoto

Uehara

Bolidong

et al. 2020

Cells

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Glycogen synthase kinase (GSK)3β is a multifunctional serine/threonine protein kinase with more than 100 substrates and interacting molecules. GSK3β is normally active in cells and negative regulation of GSK3β activity via phosphorylation of its serine 9 residue is required for most normal cells to maintain homeostasis. Aberrant expression and activity of GSK3β contributes to the pathogenesis and progression of common recalcitrant diseases such as glucose intolerance, neurodegenerative disorders and cancer. Despite recognized roles against several proto-oncoproteins and mediators of the epithelial–mesenchymal transition, deregulated GSK3β also participates in tumor cell survival, evasion of apoptosis, proliferation and invasion, as well as sustaining cancer stemness and inducing therapy resistance. A therapeutic effect from GSK3β inhibition has been demonstrated in 25 different cancer types. Moreover, there is increasing evidence that GSK3β inhibition protects normal cells and tissues from the harmful effects associated with conventional cancer therapies. Here, we review the evidence supporting aberrant GSK3β as a hallmark property of cancer and highlight the beneficial effects of GSK3β inhibition on normal cells and tissues during cancer therapy. The biological rationale for targeting GSK3β in the treatment of cancer is also discussed at length.

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“…These results indicate that these agents enhance TRAIL-induced apoptosis via multiple mechanisms in a cell type-specific manner. BIO-acetoxime is a selective inhibitor of GSK-3α/β, and its inhibition has been reported to enhance TRAIL-induced cell death [30][31][32][33][34]. CP-100356 is a P-glycoprotein inhibitor that was previously unknown as a TRAIL sensitizer.…”

Section: Discussionmentioning

confidence: 99%

Proscillaridin A Sensitizes Human Colon Cancer Cells to TRAIL-Induced Cell Death

Semba

Takamatsu

Komazawa-Sakon

et al. 2022

IJMS

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Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytotoxic cytokine that induces cancer cell death by binding to TRAIL receptors. Because of its selective cytotoxicity toward cancer cells, TRAIL therapeutics, such as recombinant TRAIL and agonistic antibodies targeting TRAIL receptors, have garnered attention as promising cancer treatment agents. However, many cancer cells acquire resistance to TRAIL-induced cell death. To overcome this issue, we searched for agents to sensitize cancer cells to TRAIL-induced cell death by screening a small-molecule chemical library consisting of diverse compounds. We identified a cardiac glycoside, proscillaridin A, as the most effective TRAIL sensitizer in colon cancer cells. Proscillaridin A synergistically enhanced TRAIL-induced cell death in TRAIL-sensitive and -resistant colon cancer cells. Additionally, proscillaridin A enhanced cell death in cells treated with TRAIL and TRAIL sensitizer, the second mitochondria-derived activator of caspase mimetic. Proscillaridin A upregulated TRAIL receptor expression, while downregulating the levels of the anti-cell death molecules, cellular FADD-like IL-1β converting enzyme-like inhibitor protein and Mcl1, in a cell type-dependent manner. Furthermore, proscillaridin A enhanced TRAIL-induced cell death partly via O-glycosylation. Taken together, our findings suggest that proscillaridin A is a promising agent that enhances the anti-cancer efficacy of TRAIL therapeutics.

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Glycogen synthase kinase-3β regulates tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-induced apoptosis via the NF-κB pathway in hepatocellular carcinoma

Cited by 4 publications

References 38 publications

MicroRNA-15a Inhibits Proliferation and Induces Apoptosis in CNE1 Nasopharyngeal Carcinoma Cells

MicroRNA-15a Inhibits Proliferation and Induces Apoptosis in CNE1 Nasopharyngeal Carcinoma Cells

Glycogen Synthase Kinase 3β in Cancer Biology and Treatment

Proscillaridin A Sensitizes Human Colon Cancer Cells to TRAIL-Induced Cell Death

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