title: Inhibition of Plk1 and Pin1 by 5'-nitro-indirubinoxime suppresses human lung cancer cells.
abstract: A novel indirubin derivative, 5'-nitro-indirubinoxime (5'-NIO), exhibits a strong anti-cancer activity against human cancer cells. Here, the 5'-NIO-mediated G1 cell cycle arrest in lung cancer cells was associated with a decrease in protein levels of polo-like kinase 1 (Plk1) and peptidyl-prolyl cis/trans isomerase Pin1. Treatment with Plk1 siRNA or Pin1 inhibitor effectively inhibited the Rb phosphorylation, suggesting their regulatory role at G1 phase. In addition, the overexpression of Plk1 or Pin1 inhibited apoptotic signals following the cleavage of PARP in 5'-NIO-treated cells. These findings suggest that 5'-NIO have potential anti-cancer efficacy through the inhibition of Plk1 or/and Pin1 expression.
authors: Department of Pathology, Chosun University College of Dentistry, Gwangju 501-759, Republic of Korea.
authors: Hyo-Eun
authors: HE
authors: Yoon
authors: Soo-A
authors: SA
authors: Kim
authors: Hong-Seok
authors: HS
authors: Choi
authors: Mee-Young
authors: MY
authors: Ahn
authors: Jung-Hoon
authors: JH
authors: Yoon
authors: Sang-Gun
authors: SG
authors: Ahn
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism; D000077192:Adenocarcinoma of Lung; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002642:Chick Embryo; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D010091:Oximes / Q000494:pharmacology*; D019696:Peptidylprolyl Isomerase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D016160:Retinoblastoma Protein / Q000378:metabolism; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D051358:Cyclin-Dependent Kinase 4; D007211:Indoles; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D010091:Oximes; D019696:Peptidylprolyl Isomerase; D011065:Poly(ADP-ribose) Polymerases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D016160:Retinoblastoma Protein; D000097869:Polo-Like Kinase 1; C534713:5'-nitroindirubinoxime; C495900:CDK4 protein, human; C000606846:PIN1 protein, human