Inhibition of protein kinase C and proto-oncogene expression by crocetin in NIH/3T3 cells.
Crocetin, a carotenoid isolated from the seeds of Gardenia jasminoides, was found to be a potent inhibitor of tumor promotion induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in mouse skin. When mouse fibroblast NIH/3T3 cells were treated with TPA alone, protein kinase C (PKC) translocated from the cytosolic fraction to the particulate fraction. Pretreatment with 60 and 120 microM crocetin for 15 min inhibited the TPA-induced PKC activity in the particulate fraction by 50% and 66%, respectively, but did not affect the level of PKC protein. Crocetin also reduced the level of TPA-stimulated phosphorylation of cellular proteins. Cells pretreated with crocetin (120 microM) had 55% less PKC [3H]phorbol dibutyrate-binding capacity. Suppression of TPA (100 ng/mL)-induced c-jun and c-fos gene expression was also observed in the mouse fibroblast cells pretreated with crocetin (30, 60, and 120 microM). Our results provided a basis for understanding the inhibitory effect of crocetin on TPA-mediated tumor promotion.
Wang
C J
CJ
Institute of Biochemistry, Chung Shan Medical and Dental College, Taichung, Taiwan, Republic of China.
Cheng
T C
TC
Liu
J Y
JY
Chou
F P
FP
Kuo
M L
ML
Lin
J K
JK
D016475:3T3 Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002273:Carcinogens; D002338:Carotenoids / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects*; D016758:Genes, jun / Q000187:drug effects*; D051379:Mice; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate; D014801:Vitamin A / Q000031:analogs & derivatives
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D004791:Enzyme Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; C487773:trans-sodium crocetinate; D014801:Vitamin A; D002338:Carotenoids; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate