alexa p27-Associated G1 arrest induced by hinokitiol in human malignant melanoma cells is mediated via down-regulation of pRb, Skp2 ubiquitin ligase, and impairment of Cdk2 function.
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Clinical & Experimental Pharmacology

Author(s): Liu S, Yamauchi H, Liu S, Yamauchi H

Abstract Share this page

Abstract Increasing evidence has confirmed that hinokitiol (beta-thujaplicin), a tropolone-related compound, exhibits anticancer activity in a variety of cancers through inhibition of cell proliferation. The present study indicates that hinokitiol selectively inhibits cell growth and DNA synthesis in FEM human melanoma cells. Hinokitiol-induced growth inhibition was associated with strong G1 cell cycle arrest. Consistent with blocking the G1-S-phase transition, hinokitiol markedly increased p27 protein levels, but caused only a moderate increase in p21, in addition to a decrease in Cdk2, cyclin E, and phosphorylated Rb. In addition, hinokitiol increased the stability of the p27 protein by inhibiting p27 phosphorylation at Thr(187) and by down-regulating Skp2 expression. siRNA knockdown of p27 abrogated hinokitiol-mediated growth inhibition, while knockdown of Skp2 exacerbated the G1 arrest. In addition to increasing Cdk inhibitor levels and decreasing cyclin A expression, hinokitiol also impaired Cdk2 function by inhibiting Cdk2 kinase activity, impeding cyclin E or A/Cdk2 binding, and inducing translocation of the Cdk2 protein complex. Taken together, our data demonstrate that the novel anticancer mechanism of hinokitiol involves accumulation of p27, down-regulation of Skp2, and impairment of Cdk2 function in FEM human melanoma cells. The therapeutic potential of hinokitiol may lead to novel cell-cycle-based anticancer strategies for malignant melanoma. This article was published in Cancer Lett and referenced in Journal of Clinical & Experimental Pharmacology

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri, Food, Aqua and Veterinary Science Journals

Dr. Krish

agrifoodaquavet@omicsonline.com

1-702-714-7001 Extn: 9040

Clinical and Biochemistry Journals

Datta A

clinical_biochem@omicsonline.com

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

business@omicsonline.com

1-702-714-7001Extn: 9042

Chemical Engineering and Chemistry Journals

Gabriel Shaw

chemicaleng_chemistry@omicsonline.com

1-702-714-7001 Extn: 9040

Earth & Environmental Sciences

Katie Wilson

environmentalsci@omicsonline.com

1-702-714-7001Extn: 9042

Engineering Journals

James Franklin

engineering@omicsonline.com

1-702-714-7001Extn: 9042

General Science and Health care Journals

Andrea Jason

generalsci_healthcare@omicsonline.com

1-702-714-7001Extn: 9043

Genetics and Molecular Biology Journals

Anna Melissa

genetics_molbio@omicsonline.com

1-702-714-7001 Extn: 9006

Immunology & Microbiology Journals

David Gorantl

immuno_microbio@omicsonline.com

1-702-714-7001Extn: 9014

Informatics Journals

Stephanie Skinner

omics@omicsonline.com

1-702-714-7001Extn: 9039

Material Sciences Journals

Rachle Green

materialsci@omicsonline.com

1-702-714-7001Extn: 9039

Mathematics and Physics Journals

Jim Willison

mathematics_physics@omicsonline.com

1-702-714-7001 Extn: 9042

Medical Journals

Nimmi Anna

medical@omicsonline.com

1-702-714-7001 Extn: 9038

Neuroscience & Psychology Journals

Nathan T

neuro_psychology@omicsonline.com

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

John Behannon

pharma@omicsonline.com

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

social_politicalsci@omicsonline.com

1-702-714-7001 Extn: 9042

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version