Inhibition of Plk1 and Pin1 by 5′-nitro-indirubinoxime suppresses human lung cancer cells

• Published in: Cancer letters Vol. 316; no. 1; pp. 97 - 104
• Main Authors: Yoon, Hyo-Eun, Kim, Soo-A, Choi, Hong-Seok, Ahn, Mee-Young, Yoon, Jung-Hoon, Ahn, Sang-Gun
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.03.2012; Elsevier Limited
• Subjects: 5′-Nitro-indirubinoxime (5′-NIO); Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adenocarcinoma of Lung; Animals; anticarcinogenic activity; Apoptosis; Apoptosis - drug effects; Apoptosis - genetics; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Cdk4; Cell cycle; Cell Cycle Checkpoints - drug effects; Cell Cycle Proteins - antagonists & inhibitors; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell Death - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Chick Embryo; Cyclin-Dependent Kinase 4 - genetics; G1 Phase - drug effects; Hematology, Oncology and Palliative Medicine; Humans; Indoles - pharmacology; interphase; Kinases; Lung cancer; lung neoplasms; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; NIMA-Interacting Peptidylprolyl Isomerase; Oximes - pharmacology; Peptidylprolyl Isomerase - antagonists & inhibitors; Peptidylprolyl Isomerase - genetics; Peptidylprolyl Isomerase - metabolism; phosphorylation; Phosphorylation - drug effects; Pin1; Plk1; Polo-Like Kinase 1; Poly(ADP-ribose) Polymerases - metabolism; Protein Serine-Threonine Kinases - antagonists & inhibitors; Protein Serine-Threonine Kinases - genetics; Protein Serine-Threonine Kinases - metabolism; Proto-Oncogene Proteins - antagonists & inhibitors; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Retinoblastoma Protein - metabolism; RNA, Small Interfering - genetics; Rb; 5′-Nitro-indirubinoxime (5′-NIO); Pin1; Plk1; Cdk4; Lung cancer
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2011.10.029

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.