AMP-activated protein kinase activators can inhibit the growth of prostate cancer cells by multiple mechanisms

Xiaoqin Xiang, Asish K. Saha, Rong Wen, Neil B. Ruderman, Zhijun Luo

Research output: Contribution to journalArticle

198 Citations (Scopus)

Abstract

Prostate cancer cells require high rates of de novo fatty acid synthesis and protein synthesis for their rapid growth. We report here that the growth of these cells is markedly diminished by incubation with activators of AMP-activated protein kinase (AMPK), a fuel-sensing enzyme that has been shown to diminish both of these processes in intact tissues. Inhibition of cell growth was observed when AMPK was activated by either 5-aminoimidazole-4-carboxamide riboside (AICAR) or the thiazolidinedione rosiglitazone. Thus, a 90% inhibition of the growth of androgen-independent (DU145, PC3) and androgen-sensitive (LNCaP) cells was achieved after 4 days of exposure to one or both of these agents. Where studied, this was associated with a decrease in the concentration of malonyl CoA, an intermediate of de novo fatty acid synthesis, and an increase in expression of the cell cycle inhibitor p21. In addition, AICAR inhibited two key enzymes involved in protein synthesis, mTOR and p70S6K, and blocked the ability of the androgen R1881 to increase cell growth and the expression of two enzymes for de novo fatty acid synthesis, acetyl CoA carboxylase and fatty acid synthase, in the LNCaP cells. The results suggest that AMPK is a potential target for the treatment of prostate cancer.

Original languageEnglish
Pages (from-to)161-167
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume321
Issue number1
DOIs
StatePublished - Aug 13 2004
Externally publishedYes

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AMP-Activated Protein Kinases
Prostatic Neoplasms
Cells
Androgens
Growth
Fatty Acids
rosiglitazone
Cell growth
Enzymes
Malonyl Coenzyme A
70-kDa Ribosomal Protein S6 Kinases
Acetyl-CoA Carboxylase
Fatty Acid Synthases
Metribolone
TOR Serine-Threonine Kinases
Proteins
Tissue
Cell Cycle

Keywords

  • Acetyl CoA carboxylase
  • AMP-activated protein kinase
  • Fatty acid synthase
  • Growth
  • mTOR
  • p21
  • p70S6K
  • Prostate cancer cell
  • Survival

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

AMP-activated protein kinase activators can inhibit the growth of prostate cancer cells by multiple mechanisms. / Xiang, Xiaoqin; Saha, Asish K.; Wen, Rong; Ruderman, Neil B.; Luo, Zhijun.

In: Biochemical and Biophysical Research Communications, Vol. 321, No. 1, 13.08.2004, p. 161-167.

Research output: Contribution to journalArticle

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