Academic Journal
Enantiomerically pure beta-dipeptide derivative induces anticancer activity against human hormone-refractory prostate cancer through both PI3K/Akt-dependent and -independent pathways
| العنوان: | Enantiomerically pure beta-dipeptide derivative induces anticancer activity against human hormone-refractory prostate cancer through both PI3K/Akt-dependent and -independent pathways |
|---|---|
| المؤلفون: | Chan, Mei-Ling, Yu, Chia-Chun, Hsu, Jui-Ling, Leu, Wohn-Jenn, Chan, She-Hung, Hsu, Lih-Ching, Liu, Shih-Ping, Ivantcova, Polina M., Doğan, Özdemir, Braese, Stefan, KUDRYAVTSEV, Konstantin V, GUH, Jih Hwa |
| بيانات النشر: | Impact Journals, LLC ONCOTARGET |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Oncology |
| الوصف: | The use of peptides that target cancer cells and induce anticancer activities through various mechanisms is developing as a potential anticancer strategy. KUD983, an enantiomerically pure beta-dipeptide derivative, displays potent activity against hormone-refractory prostate cancer (HRPC) PC-3 and DU145 cells with submicromolar IC50. KUD983 induced G1 arrest of the cell cycle and subsequent apoptosis associated with down-regulation of several related proteins including cyclin D1, cyclin E and Cdk4, and the de-phosphorylation of RB. The levels of nuclear and total c-Myc protein, which could increase the expression of both cyclin D1 and cyclin E, were profoundly inhibited by KUD983. Furthermore, it inhibited PI3K/Akt and mTOR/p70S6K/4E-BP1 pathways, the key signaling in multiple cellular functions. The transient transfection of constitutively active myristylated Akt (myr-Akt) cDNA significantly rescued KUD983induced caspase activation but did not blunt the inhibition of mTOR/p7056K/4E-BP1 signaling cascade suggesting the presence of both Akt-dependent and -independent pathways. Moreover, KUD983-induced effect was enhanced with the down-regulation of anti-apoptotic Bcl-2 members (e.g., Bcl-2, and Mcl-1) and IAP family members (e.g., survivin). Notably, KUD983 induced autophagic cell death using confocal microscopic examination, tracking the level of conversion of LC3-I to LC3-II and flow cytometric detection of acidic vesicular organelles-positive cells. In conclusion, the data suggest that KUD983 is an anticancer beta-dipeptide against HRPCs through the inhibition of cell proliferation and induction of apoptotic and autophagic cell death. The suppression of signaling pathways regulated by c-Myc, PI3K/Akt and mTOR/p7056K/4E-BP1 and the collaboration with down-regulation of Mcl-1 and survivin may explain KUD983-induced anti-HRPC mechanism. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| ردمك: | 978-85-03-37813-0 85-03-37813-2 |
| تدمد: | 1949-2553 |
| Relation: | Chan M., Yu C., Hsu J., Leu W., Chan S., Hsu L., Liu S., Ivantcova P. M. , DOĞAN Ö., Braese S., et al., "Enantiomerically pure beta-dipeptide derivative induces anticancer activity against human hormone-refractory prostate cancer through both PI3K/Akt-dependent and -independent pathways", ONCOTARGET, cilt.8, ss.96668-96683, 2017; 96683; 57; 85033781327; 96668; https://hdl.handle.net/11511/47434; WOS:000419395000026 |
| DOI: | 10.18632/oncotarget.18040 |
| الاتاحة: | https://hdl.handle.net/11511/47434 https://doi.org/10.18632/oncotarget.18040 |
| Rights: | Attribution-NonCommercial-NoDerivatives 4.0 International ; http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| رقم الانضمام: | edsbas.B6080438 |
| قاعدة البيانات: | BASE |
Full Text Finder | ردمك: | 9788503378130 8503378132 |
|---|---|
| تدمد: | 19492553 |
| DOI: | 10.18632/oncotarget.18040 |