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http://ir.nhri.org.tw/handle/3990099045/3390
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| Title: | Mana-Hox displays anticancer activity against prostate cancer cells through tubulin depolymerization and DNA damage stress |
| Authors: | Hsiao, CJ;Ho, YF;Hsu, JTA;Chang, WL;Chen, YC;Shen, YC;Lyu, PC;Guh, JH |
| Contributors: | Division of Biotechnology and Pharmaceutical Research |
| Abstract: | Tubulin and deoxyribonucleic acid (DNA) are two potential targets for the development of cancer chemotherapeutic agents. Mana-Hox is a synthetic derivative of β-carboline, a structure relevant to marine sponge component, manzamine. In this study, Mana-Hox induced an inhibition of cell proliferation in several types of human cancer cell lines, including androgen-independent prostate cancer PC-3 and DU-145, hepatocellular carcinoma Hep3B and HepG2, and colorectal cancer HT-29 cells. The p53-null PC-3 cells were used for to anticancer mechanisms. Mana-Hox stimulated an increase of ataxia telangiectasia mutated (ATM) phosphorylation on Ser-1981, indicating the induction of DNA double-strand breaks. It also displayed an inhibitory effect on tubulin polymerization using tubulin turbidity assay and immunofluorescence identification. However, it only showed a minor inhibition on the activity of Aurora kinase and histone deacetylase. Mana-Hox induced mitotic arrest of the cell cycle identified by downregulation of cyclin E, cyclin A, and cyclin-dependent kinase 2 (Cdk2) and an increase of MPM-2 expression. Next, it caused Bcl-2 phosphorylation on Ser-70, downregulation of Mcl-1 expression, and activation of caspase-3, leading to apoptotic cell death. Notably, Mana-Hox was not a P-glycoprotein (P-gp) substrate and showed equipotent activity against P-gp-rich cancer cells. We conclude that Mana-Hox induces dual effects on DNA damage and tubulin depolymerization, leading to mitotic arrest and activation of mitochondria-mediated apoptotic pathways. Data provide evidence that the anticancer strategy of dual-action targets could be a potential anticancer approach. ? 2008 Springer-Verlag. |
| Date: | 2008-12 |
| Relation: | Naunyn-Schmiedeberg's Archives of Pharmacology. 2008 Dec;378(6):599-608. |
| Link to: | http://dx.doi.org/10.1007/s00210-008-0330-7 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0028-1298&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000261036700005 |
| Cited Times(Scopus): | http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=56549120781 |
| Appears in Collections: | [徐祖安] 期刊論文
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| SCP56549120781.pdf | | 374Kb | Adobe PDF | 439 | View/Open |
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