Growth attenuation in a human prostate cell line mediated by a phorbol ester.
Human prostatic cancer cells JCA-1 were induced with a phorbol ester 12-o-tetradecanoylphorbol-13-acetate (TPA), and cell growth differentiation were analyzed. Within hours of exposure to TPA, cell proliferation decreased and reached approximately 80% reduction after 3 days, as determined by [3H]thymidine incorporation and cell counting. Cell cycle analysis revealed a blocking of cells entering into the replicating S and G2M phases from the G1 phase. The TPA induced cells had a reduced growth rate but remained viable. The growth-modulating activity of TPA was similarly observed with LNCaP cells. Agarose gel electrophoresis of the chromosomal DNA from induced cells exhibited a non-fragmented pattern excluding the possibility of cell apoptosis. In parallel to the growth reduction, the TPA induced cells became larger in size showing dendrite like cytoplasmic extensions. Furthermore, JCA-1 cells treated with TPA acquired the expression of cytokeratin 18 and increased the expression of actin and vimentin by 300%. These results indicate an induced growth reduction accompanied by cellular differentiation of the prostatic cancer cells.
Novichenko
N
N
Department of Medicine, New York Medical College, Valhalla 10595, USA.
Konno
S
S
Nakajima
Y
Y
Hsieh
T C
TC
Xu
W
W
Turo
K
K
Ahmed
T
T
Chiao
J W
JW
D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D011467:Prostate / Q000166:cytology* / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D003598:Cytoskeletal Proteins; D016326:Extracellular Matrix Proteins; D013755:Tetradecanoylphorbol Acetate