Inhibition of protein kinase C and proto-oncogene expression by crocetin in NIH/3T3 cells

Abstract

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.

Anti‐tumor effects of crocetin and related molecular targets

“…The results showed that crocetin inhibits c‐Jun, c‐Fos, and c‐Myc gene expression in NIH/3T3 cells. Crocetin also inhibits H 2 O 2 , myeloperoxidase and PKC activity in TPA‐induced skin tumor in mice, but no effect was observed on PKC protein level (Wang, Lee, Chang, & Lin, ; Wang et al, ). It was shown that oral administration of SE (200 mg/kg) inhibits the growth of ascite tumors derived from S‐180, EAC, and DLA in a dose‐dependent manner, and significantly elevated (2‐ to 3‐fold) life spans of treated tumor‐bearing Swiss albino mice.…”

Pharmacological Properties of Crocetin and Crocin (Digentiobiosyl Ester of Crocetin) from Saffron

“…The authors suggest that crocetin suppressed TPAinduced skin carcinogenesis, probably through its antioxidant property, leading in turn to a reduction in TPA-induced expressions of oncoproteins [52]. In vitro, crocetin significantly inhibits TPA-induced translocation of protein kinase C (PKC) from the cytosolic fraction to the particulate fraction, phosphorylation of cellular proteins, and c-jun and cfos gene expression in mouse fibroblast NIH/3T3 cells [53]. In addition, local application of crocetin markedly restricts TPA-induced promotion of skin tumors, and hyperplasia and edema initiated in mouse ear with benzo[a]pyrene (BP).…”

Therapeutic potential of saffron, and its chemical components in the treatment of cancers and cardiovascular disorders – a review

“…Liu et al (2020)CrocinMale Sprague Dawley rats Reduction of experimentally-induced hepatocellular carcinoma through modulating the oxidative/apoptotic pathway. Crocin-induced hepatic expression of Nrf2 improved downstream modifications in KEAP-1 and HO-1 signalling pathway.Elsherbiny et alCrocin delayed papilloma's formation in mice .Konoshima et al (1998)Crocetin Mice fibroblast NIH/3T3 cells 120 and 60 µM crocetin inhibited the activity of TPA-induced protein kinase C by 66 and 50%, respectively Wang et al (1996). Aqueous saffron extract Female Swiss albino mice Saffron treatment before and after DMBA application reduced papilloma formation Das et al (2004;.…”