PPAR-gamma ligands and amino acid deprivation promote apoptosis of melanoma, prostate, and breast cancer cells.
The PPAR-gamma ligands, 15-deoxy-Delta(12,14)-prostaglandin J(2) and ciglitazone, and the PPAR-alpha ligand, WY-14643, were examined for their effects on proliferation and apoptosis of A375 melanoma, DU145 and PC3 prostate cancer, and MB-MDA-231 breast cancer. While 15-deoxy-Delta(12,14)-prostaglandin J(2) inhibited proliferation of A375 melanoma, ciglitazone was inactive against this and the other cell lines. Restriction of specific amino acids known to inhibit proliferation and induce apoptosis sensitized all cell lines to ciglitazone, and the combined effects were greater than the individual effects of either treatment. WY-14643 alone or in combination with amino acid deprivation was inactive. Normal fibroblasts were resistant to the treatments.
Cancer Prevention & Research Center, The Pharmacology and Toxicology Graduate Program, Department of Pharmaceutical Sciences, and the College of Pharmacy, Washington State University, Pullman, WA 99164-6713, USA.
Nomelí P
NP
Núñez
Huaitian
H
Liu
Gary G
GG
Meadows
D000596:Amino Acids / Q000172:deficiency*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007155:Immunologic Factors / Q000494:pharmacology; D008024:Ligands; D008297:Male; D008545:Melanoma; D008715:Methionine / Q000172:deficiency; D047495:PPAR gamma / Q000378:metabolism*; D010649:Phenylalanine / Q000172:deficiency; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D011471:Prostatic Neoplasms; D045162:Thiazolidinediones / Q000494:pharmacology*; D014443:Tyrosine / Q000172:deficiency
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D000596:Amino Acids; D000970:Antineoplastic Agents; D007004:Hypoglycemic Agents; D007155:Immunologic Factors; D008024:Ligands; D047495:PPAR gamma; D045162:Thiazolidinediones; D014443:Tyrosine; D010649:Phenylalanine; D008715:Methionine; D015230:Prostaglandin D2; C039671:ciglitazone