Apoptosis of androgen-independent prostate cell line induced by inhibition of fatty acid synthesis.
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.
Furuya
Y
Y
Department of Urology, School of Medicine, Chiba University, Japan.
Akimoto
S
S
Yasuda
K
K
Ito
H
H
D000728:Androgens / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D018797:Cell Cycle Proteins; D002569:Cerulenin / Q000494:pharmacology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D016213:Cyclins / Q000096:biosynthesis; D053938:DNA Fragmentation; D004273:DNA, Neoplasm / Q000032:analysis / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors*; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D011471:Prostatic Neoplasms; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D000728:Androgens; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004273:DNA, Neoplasm; D004791:Enzyme Inhibitors; D008869:Microtubule-Associated Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D002569:Cerulenin; D064429:Fatty Acid Synthases; D018844:Cyclin-Dependent Kinases