Inactive caspase 3 activates Akt in human leukemia cells susceptible or resistant to apoptosis induced by phorbol ester

Hah, Jeong-Ok; Lee, Kyung‐Ah; Choi, Yun Jung; Kim, Won-Duck; Park, Jong‐Wook; Kwon, Taeg Kyu

doi:10.3892/ijo.22.5.1111

Cited by 2 publications

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“…5A). PMA is a potent inducer for a number of important cell signaling pathways, including the PI3K-AKT pathway (39). It has been reported that AKT activation stabilizes XIAP through enhanced phosphorylation and suppressed ubiquitination and proteasomal degradation (33).…”

Section: Discussionmentioning

confidence: 99%

Protein Kinase C Inhibition and X-Linked Inhibitor of Apoptosis Protein Degradation Contribute to the Sensitization Effect of Luteolin on Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand–Induced Apoptosis in Cancer Cells

Ong¹,

Shen²

2005

Cancer Research

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Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is an important member of the TNF superfamily with great potential in cancer therapy. Luteolin is a dietary flavonoid commonly found in some medicinal plants.Here we found that pretreatment with a noncytotoxic concentration of luteolin significantly sensitized TRAILinduced apoptosis in both TRAIL-sensitive (HeLa) and TRAIL-resistant cancer cells (CNE1, HT29, and HepG2). Such sensitization is achieved through enhanced caspase-8 activation and caspase-3 maturation. Further, the protein level of X-linked inhibitor of apoptosis protein (XIAP) was markedly reduced in cells treated with luteolin and TRAIL, and ectopic expression of XIAP protected against cell death induced by luteolin and TRAIL, showing that luteolin sensitizes TRAIL-induced apoptosis through down-regulation of XIAP. In search of the molecular mechanism responsible for XIAP down-regulation, we found that luteolin and TRAIL promoted XIAP ubiquitination and proteasomal degradation. Next, we showed that protein kinase C (PKC) activation prevented cell death induced by luteolin and TRAIL via suppression of XIAP down-regulation. Moreover, luteolin inhibited PKC activity, and bisindolylmaleimide I, a general PKC inhibitor, simulated luteolin in sensitizing TRAILinduced apoptosis. Taken together, these results present a novel anticancer effect of luteolin and support its potential application in cancer therapy in combination with TRAIL. In addition, our data reveal a new function of PKC in cell death: PKC activation stabilizes XIAP and thus suppresses TRAIL-induced apoptosis. (Cancer Res 2005; 65(17): 7815-23)

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Section: Discussionmentioning

confidence: 99%

Protein Kinase C Inhibition and X-Linked Inhibitor of Apoptosis Protein Degradation Contribute to the Sensitization Effect of Luteolin on Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand–Induced Apoptosis in Cancer Cells

Ong¹,

Shen²

2005

Cancer Research

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“…Esses efeitos, em conjunto, contribuem para a proliferação celular e não permitem que a célula caminhe para a morte celular programada DATTA et al, 1997;GREENBERG, 1999;HAH et al, 2003;SÖDERLUNG;PÉREZ-TENÓTIO;STÄL, 2005;VESTEY et al, 2005;ZHANG et al, 2007 Já está estabelecido, também, na literatura a interação existente entre NF-kB e a proteína p53. Antagonismo das funções de transcrição que ocorre entre p53 e NF-κB envolve competição com co-ativadores como p300 e CBP (do inglês CREBbinding protein).…”

Section: Distribuição Da Recidiva Conforme a Presença De Paktunclassified

Avaliação imunoistoquímica das proteínas metalotioneína, pAKT e NF-kB como marcadores de prognóstico de carcinomas epidermóides de boca

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Inactive caspase 3 activates Akt in human leukemia cells susceptible or resistant to apoptosis induced by phorbol ester

Cited by 2 publications

References 0 publications

Protein Kinase C Inhibition and X-Linked Inhibitor of Apoptosis Protein Degradation Contribute to the Sensitization Effect of Luteolin on Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand–Induced Apoptosis in Cancer Cells

Protein Kinase C Inhibition and X-Linked Inhibitor of Apoptosis Protein Degradation Contribute to the Sensitization Effect of Luteolin on Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand–Induced Apoptosis in Cancer Cells

Avaliação imunoistoquímica das proteínas metalotioneína, pAKT e NF-kB como marcadores de prognóstico de carcinomas epidermóides de boca

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