Apoptosis of androgen-independent prostate cell line induced by inhibition of fatty acid synthesis

Anticancer Res. Nov-Dec 1997;17(6D):4589-93.

Abstract

Androgen-dependent prostate cancer cells eventually progress to androgen -independent cells after hormonal manipulation. Due to chemotherapeutic drug resistance and toxic side effects, new targets for antineoplastic therapy are urgently needed. In the present study, cerulenin, a fatty acid synthase inhibitor, was used to induce the death of androgen-independent prostate cancer cells. Cerulenin induces the apoptosis of TSU-prl cells based upon the temporal sequence of DNA fragmentation, morphologic changes and loss of cell viability. During apoptotic process induced by the agents, expression of cyclin-dependent kinase inhibitors p21 and p27 increased, whereas expression of cyclin D1 decreased. Flow cytometric analysis showed that the treatment resulted in a block in G2/M of the cell cycle. These results demonstrated that inhibition of fatty acid synthesis could be a target to treat hormone-independent prostate cancer cells via apoptosis, and cyclin-dependent kinase inhibitors played some role during apoptotic pathway.

MeSH terms

  • Androgens / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Cell Cycle Proteins*
  • Cerulenin / pharmacology*
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclin-Dependent Kinases / antagonists & inhibitors
  • Cyclins / biosynthesis
  • DNA Fragmentation
  • DNA, Neoplasm / analysis
  • DNA, Neoplasm / drug effects
  • Enzyme Inhibitors / pharmacology
  • Fatty Acid Synthases / antagonists & inhibitors*
  • Humans
  • Male
  • Microtubule-Associated Proteins / biosynthesis
  • Prostatic Neoplasms
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins*

Substances

  • Androgens
  • CDKN1A protein, human
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • DNA, Neoplasm
  • Enzyme Inhibitors
  • Microtubule-Associated Proteins
  • Tumor Suppressor Proteins
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cerulenin
  • Fatty Acid Synthases
  • Cyclin-Dependent Kinases