13-cis-retinoic acid-mediated growth inhibition of DU-145 human prostate cancer cells.
The purpose of this study was to examine the effects of 13-cis-retinoic acid (13-cis-RA) on the growth regulation of DU-145 human prostatic cancer cells. The results of these experiments demonstrate that cell growth and metastatic potential of DU-145 cells were significantly inhibited by 13-cis-RA (10 microM). In order to elucidate the possible molecular mechanisms of 13-cis-RA action on prostate cancer cells, we examined the expression of nuclear receptor genes (hRXR alpha) and found that 13-cis-RA treated cells showed higher mRNA expression for hRXR alpha nuclear receptors compared to untreated cells. To elucidate further the possible biochemical mechanisms associated with these alterations, we analyzed the phosphorous metabolites by MR spectroscopy and found that the major metabolites were PME, (PC, PE) and DPDE (UDP-GalNAc, UDP-GLcNAc). The DU-145 cells and xenografts, which were both treated with 13-cis-RA, showed a two-fold decrease in DPDE's, compared to their controls. The higher resolution spectra of perfused cells revealed that phosphocholine levels were twice as high in 13-cis-RA-treated DU-145 cells as compared to untreated cells. These investigations demonstrate for the first time that 13-cis-RA inhibits the growth of human prostatic cancer cells, and this inhibition is associated with an increase in hRXR alpha nuclear receptor gene expression and alterations in phosphorous metabolites detected by 31P MR spectroscopy.
Department of Urology, University of California, School of Medicine, San Francisco.
R
R
Dahiya
B
B
Boyle
H D
HD
Park
J
J
Kurhanewicz
J M
JM
Macdonald
P
P
Narayan
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D017364:Collagenases / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D015474:Isotretinoin / Q000494:pharmacology*; D007797:Laminin / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D020780:Matrix Metalloproteinase 9; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured
D005353:Fibronectins; D007797:Laminin; D018168:Receptors, Retinoic Acid; D003094:Collagen; D017364:Collagenases; D020780:Matrix Metalloproteinase 9; D015474:Isotretinoin