EurekaMag.com logo
+ Site Statistics
References:
53,517,315
Abstracts:
29,339,501
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on Google+Follow on Google+
Follow on LinkedInFollow on LinkedIn

+ Translate

The Akt inhibitor KP372-1 inhibits proliferation and induces apoptosis and anoikis in squamous cell carcinoma of the head and neck



The Akt inhibitor KP372-1 inhibits proliferation and induces apoptosis and anoikis in squamous cell carcinoma of the head and neck



Oral Oncology 42(4): 430-439



Therapies that target signaling pathways critical to the pathogenesis and progression of squamous cell carcinoma of the head and neck (HNSCC) are needed. One such target, phosphatidylinositol 3-kinase, and its downstream target serine/threonine kinase, Akt, are up-regulated in HNSCC. Targeted therapy could consist of inhibitors of these kinases or, alternatively, of inhibitors of the pathways that they regulate. To explore the effect of Akt inhibition on the growth and survival of HNSCC tumors, we evaluated the effect of a novel Akt inhibitor, KP372-1, on the growth, survival, and sensitivity to anoikis of HNSCC cell lines in culture. Using Western blotting of head and neck cancer cell tines and squamous mucosa and carcinoma specimens, we found that Akt was highly phosphorylated in head and neck cancer cell lines and human head and neck squamous carcinoma specimens. Treatment of HNSCC cell tines with KP372-1 blocked the activation of Akt, inhibited head and neck cancer cell proliferation, and induced apoptosis and anoikis in several HNSCC cell lines. Furthermore, KP372-1 decreased the phosphorylation of the S6 ribosomal (Ser240/244) protein, which is a downstream target of Akt. Taken together, these findings indicate that KP372-1 may be a useful therapeutic agent for HNSCC and should be further evaluated in preclinical models of HNSCC. (c) 2005 Elsevier Ltd. All rights reserved.

(PDF same-day service: $19.90)

Accession: 012627094

Download citation: RISBibTeXText

PMID: 16442835

DOI: 10.1016/j.oraloncology.2005.09.011



Related references

Sulindac induces apoptosis and inhibits tumor growth in vivo in head and neck squamous cell carcinoma. Neoplasia 9(3): 192-199, 2007

The farnesyltransferase inhibitor SCH66336 induces apoptosis through down-regulation of AKT signaling pathway in human head and neck squamous cell carcinoma cell lines. Proceedings of the American Association for Cancer Research Annual Meeting 43: 813, March, 2002

Targeting HOTAIR Induces Mitochondria Related Apoptosis and Inhibits Tumor Growth in Head and Neck Squamous Cell Carcinoma in vitro and in vivo. Current Molecular Medicine 15(10): 952-960, 2016

Cyclin-dependent kinase inhibitor (roscovitine) suppresses growth and induces apoptosis by regulating Bcl-x in head and neck squamous cell carcinoma cells. International Journal of Oncology 21(1): 95-101, 2002

The Akt inhibitor KP372-1 suppresses Akt activity and cell proliferation and induces apoptosis in thyroid cancer cells. British Journal of Cancer 92(10): 1899-1905, 2005

Hepatocyte growth factor inhibits anoikis in head and neck squamous cell carcinoma cells by activation of ERK and Akt signaling independent of NFkappa B. Journal of Biological Chemistry 277(28): 25203-8, 2002

Dasatinib (BMS-354825) tyrosine kinase inhibitor suppresses invasion and induces cell cycle arrest and apoptosis of head and neck squamous cell carcinoma and non-small cell lung cancer cells. Clinical Cancer Research 11(19 Pt 1): 6924-6932, 2005

Proteasome inhibitor PS-341 induces apoptosis through induction of endoplasmic reticulum stress-reactive oxygen species in head and neck squamous cell carcinoma cells. Molecular and Cellular Biology 24(22): 9695-9704, 2004

Hepatocyte growth factor inhibits anoikis by induction of activator protein 1-dependent cyclooxygenase-2. Implication in head and neck squamous cell carcinoma progression. Journal of Biological Chemistry 277(51): 50137-50142, 2002

Promoter methylation of MGMT, MLH1 and RASSF1A tumor suppressor genes in head and neck squamous cell carcinoma: pharmacological genome demethylation reduces proliferation of head and neck squamous carcinoma cells. Oncology Reports 27(4): 1135-1141, 2012

Lycopene inhibits the cell proliferation and invasion of human head and neck squamous cell carcinoma. Molecular Medicine Reports 14(4): 2953-2958, 2016

Cyclin D1 expression in squamous cell carcinoma of head and neck correlates with both proliferation and apoptosis. Proceedings of the American Association for Cancer Research Annual Meeting 37(0): 209, 1996

Celecoxib inhibits cell proliferation through the activation of ERK and p38 MAPK in head and neck squamous cell carcinoma cell lines. Anti-Cancer Drugs 21(9): 823-830, 2010

Bcl-xL inhibits p53- but not apoptin-induced apoptosis in head and neck squamous cell carcinoma cell line. International Journal of Cancer 109(1): 38-42, 2004