The Akt inhibitor KP372-1 suppresses Akt activity and cell proliferation and induces apoptosis in thyroid cancer cells

M. Mandal, S. Kim, M. N. Younes, S. A. Jasser, A. K. El-Naggar, Gordon Mills, J. N. Myers

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

The phosphatidylinositol 3′ kinase (PI3K)/phosphatase and tensin homologue deleted on chromosome ten/Akt pathway, which is a critical regulator of cell proliferation and survival, is mutated or activated in a wide variety of cancers. Akt appears to be a key central node in this pathway and thus is an attractive target for targeted molecular therapy. We demonstrated that Akt is highly phosphorylated in thyroid cancer cell lines and human thyroid cancer specimens, and hypothesised that KP372-1, an Akt inhibitor, would block signalling through the PI3K pathway and inhibit cell proliferation while inducing apoptosis of thyroid cancer cells, KP372-1 blocked signalling downstream of Akt in thyroid tumour cells, leading to inhibition of cell proliferation and increased apoptosis. As thyroid cancer consistently expresses phosphorylated Akt and KP372-1 effectively blocks Akt signalling, further preclinical evaluation of this compound for treatment of thyroid cancer is warranted.

Original languageEnglish (US)
Pages (from-to)1899-1905
Number of pages7
JournalBritish Journal of Cancer
Volume92
Issue number10
DOIs
StatePublished - May 23 2005
Externally publishedYes

Fingerprint

Thyroid Neoplasms
Cell Proliferation
Apoptosis
Phosphatidylinositol 3-Kinase
Molecular Targeted Therapy
Phosphoric Monoester Hydrolases
Neoplasms
Cell Survival
Thyroid Gland
Chromosomes
KP372-1
Cell Line
Therapeutics

Keywords

  • Anaplastic thyroid cancer
  • Growth factors
  • KP372-1
  • Molecular therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

The Akt inhibitor KP372-1 suppresses Akt activity and cell proliferation and induces apoptosis in thyroid cancer cells. / Mandal, M.; Kim, S.; Younes, M. N.; Jasser, S. A.; El-Naggar, A. K.; Mills, Gordon; Myers, J. N.

In: British Journal of Cancer, Vol. 92, No. 10, 23.05.2005, p. 1899-1905.

Research output: Contribution to journalArticle

Mandal, M. ; Kim, S. ; Younes, M. N. ; Jasser, S. A. ; El-Naggar, A. K. ; Mills, Gordon ; Myers, J. N. / The Akt inhibitor KP372-1 suppresses Akt activity and cell proliferation and induces apoptosis in thyroid cancer cells. In: British Journal of Cancer. 2005 ; Vol. 92, No. 10. pp. 1899-1905.
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