alpha-Lipoic acid prevents p53 degradation in colon cancer cells by blocking NF-kappa B induction of RPS6KA4
DC Field | Value | Language |
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dc.contributor.author | Yoo, Tae-Hyoung | - |
dc.contributor.author | Lee, Jin-Hee | - |
dc.contributor.author | Chun, Hyang-Sook | - |
dc.contributor.author | Chi, Sung-Gil | - |
dc.date.accessioned | 2021-09-06T00:22:56Z | - |
dc.date.available | 2021-09-06T00:22:56Z | - |
dc.date.created | 2021-06-14 | - |
dc.date.issued | 2013-07 | - |
dc.identifier.issn | 0959-4973 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/102897 | - |
dc.description.abstract | alpha-Lipoic acid (alpha-LA) is a biogenic antioxidant that has been used successfully in the treatment of diabetic polyneuropathy and its application to many oxidative stress-associated chronic diseases has increased. In this study, we investigated the effect of alpha-LA on colorectal cancer cell growth and its underlying mechanism. alpha-LA treatment resulted in a marked reduction in the growth of HCT116 colon cancer cells in a dose-dependent manner through the G(1) arrest of the cell cycle and apoptosis induction. alpha-LA treatment significantly increased tumor cell response to various apoptotic stresses, such as etoposide, 5-fluorouracil, UVC, gamma-irradiation, hypoxia, and tumor necrosis factor alpha(TNF alpha). Interestingly, alpha-LA increased p53 protein stability and its apoptosis-enhancing effect was more evident in wild-type p53-carrying cells compared with p53-deficient cells, suggesting that the proapoptotic role of alpha-LA is associated with its p53-stabilizing function. On the basis of our microarray data showing alpha-LA downregulation of the ribosomal protein p90S6K (RPS6KA4), which has been reported to inhibit p53 function, we tested whether alpha-LA regulation of RPS6KA4 is associated with its proapoptotic function. alpha-LA treatment led to a marked reduction in the RPS6KA4 mRNA level in multiple colorectal cancer cells and restoration of RPS6KA4 expression markedly attenuated alpha-LA induction of apoptosis in a p53-dependent manner. In addition, we observed that RPS6KA4 expression is activated by TNF alpha whereas both basal and TNF alpha induction of RPS6KA4 are inhibited by the nuclear factor-kappa B (NF-kappa B) inhibitor BAY11-7082 or transfection of a dominant-negative mutant of NF-kappa B, indicating that NF-kappa B plays a crucial role in RPS6KA4 gene expression. Finally, we found that alpha-LA exerts an inhibitory effect on the nuclear translocation of NF-kappa B triggered by TNF alpha. Collectively, our study shows that alpha-LA suppresses colorectal tumor cell growth at least partially by preventing RPS6KA4-mediated p53 inhibition through blockade of NF-kappa B signaling. (c) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | LIPPINCOTT WILLIAMS & WILKINS | - |
dc.subject | TUMOR-NECROSIS-FACTOR | - |
dc.subject | INDUCED APOPTOSIS | - |
dc.subject | S6 KINASE | - |
dc.subject | ANTIOXIDANT | - |
dc.subject | ACTIVATION | - |
dc.subject | MURINE | - |
dc.title | alpha-Lipoic acid prevents p53 degradation in colon cancer cells by blocking NF-kappa B induction of RPS6KA4 | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Chi, Sung-Gil | - |
dc.identifier.doi | 10.1097/CAD.0b013e32836181eb | - |
dc.identifier.scopusid | 2-s2.0-84878951705 | - |
dc.identifier.wosid | 000323214000002 | - |
dc.identifier.bibliographicCitation | ANTI-CANCER DRUGS, v.24, no.6, pp.555 - 565 | - |
dc.relation.isPartOf | ANTI-CANCER DRUGS | - |
dc.citation.title | ANTI-CANCER DRUGS | - |
dc.citation.volume | 24 | - |
dc.citation.number | 6 | - |
dc.citation.startPage | 555 | - |
dc.citation.endPage | 565 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.subject.keywordPlus | TUMOR-NECROSIS-FACTOR | - |
dc.subject.keywordPlus | INDUCED APOPTOSIS | - |
dc.subject.keywordPlus | S6 KINASE | - |
dc.subject.keywordPlus | ANTIOXIDANT | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | MURINE | - |
dc.subject.keywordAuthor | alpha-Lipoic acid | - |
dc.subject.keywordAuthor | apoptosis | - |
dc.subject.keywordAuthor | colon cancer | - |
dc.subject.keywordAuthor | p53 | - |
dc.subject.keywordAuthor | RPS6KA4 | - |
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