Effects of the calcium influx inhibitor carboxyamido-triazole on the proliferation and invasiveness of human prostate tumor cell lines.
Aberrant cellular signaling is a central feature of malignant cells and a potential target for anti-cancer therapy. Carboxyamido-triazole (CAI) is a calcium influx inhibitor that alters calcium-sensitive signal transduction pathways and suppresses the proliferative and metastatic potential of malignant cells. We have examined the effects of CAI on several tumor-associated parameters in human prostate cancer cell lines to evaluate the potential of CAI as a signal-transduction therapy agent for advanced-stage prostate cancer. Measuring anchorage-dependent cell growth, continuous application of CAI inhibited the growth of DU-145, PPC-1, PC3 and LNCaP tumor cells with 50% inhibitory concentrations ranging 10-30 microM. Direct cell enumeration assays revealed that the growth-suppressing activity of CAI toward DU-145 cells was reversible, indicating a cytostatic effect of the drug on tumor cells. The drug also inhibited the proliferation of several immortalized human prostatic epithelial cell lines. The proliferation of HaCaT- and RHEK-1-immortalized keratinocyte cell lines was relatively insensitive to CAI. Additionally, invasion by DU-145, PC3 and PPC-1 cells through Matrigel in vitro was reduced approximately 60-70% by 10 microM CAI. Other cellular effects of CAI included an attenuation of the elevation of intracellular free calcium in response to bombesin and carbachol in PC3 cells and a marked dose-dependent inhibition of prostate-specific antigen secretion in LNCaP cell cultures.
Wasilenko
W J
WJ
Department of Microbiology and Immunology, Eastern Virginia Medical School, Norfolk 23507, USA.
Palad
A J
AJ
Somers
K D
KD
Blackmore
P F
PF
Kohn
E C
EC
Rhim
J S
JS
Wright
G L
GL
Schellhammer
P F
PF
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D014230:Triazoles / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D000970:Antineoplastic Agents; D014230:Triazoles; C062058:carboxyamido-triazole; D017430:Prostate-Specific Antigen; D002118:Calcium