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Delphinidin attenuates neoplastic transformation in JB6 Cl41 mouse epidermal cells by blocking Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signaling


, : Delphinidin attenuates neoplastic transformation in JB6 Cl41 mouse epidermal cells by blocking Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signaling. Cancer Prevention Research 1(7): 522-531

Recent studies suggest that anthocyanidins play a pivotal role in the chemopreventive effects of fruits and vegetables. However, the underlying molecular mechanisms and cellular targets remain unknown. Neoplastic transformation of cells and inflammation are considered to be major events contributing to carcinogenesis. Here, we report that delphinidin, a major dietary anthocyanidin, inhibits tumor promoter-induced transformation and cyclooxygenase-2 (COX-2) expression in JB6 promotion-sensitive mouse skin epidermal (JB6 P+) cells by directly targeting Raf and mitogen-activated protein kinase kinase (MEK). Delphinidin inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced neoplastic transformation and COX-2 expression at both the protein and transcriptional levels. The activation of activator protein-1 and nuclear factor-kappaB induced by TPA was dose dependently inhibited by delphinidin treatment. Delphinidin strongly suppressed Raf1 and MEK1 kinase activities and subsequently attenuated TPA-induced phosphorylation of MEK, extracellular signal-regulated kinase (ERK), p90RSK, and MSK. Although delphinidin suppressed ERK and c-Jun NH(2)-terminal kinase activities, it was more effective at inhibiting Raf1 or MEK1 activities. Pull-down and competition assays revealed that delphinidin binds with Raf1 or MEK1 noncompetitively with ATP. Delphinidin also dose dependently suppressed JB6 P+ cell transformation induced by epidermal growth factor and H-Ras, both of which are involved in the activation of Raf/MEK/ERK signaling. Together, these findings suggested that the targeted inhibition of Raf1 and MEK activities and COX-2 expression by delphinidin contribute to the chemopreventive potential of fruits and vegetables.

US$19.90

PMID: 19139002

DOI: 10.1158/1940-6207.CAPR-08-0071


Other references

Anonymous., 1973: Essex bird report, 1973. Essex Bird Rep, 5-50

Hosono A.; Sagae S.; Tokita F., 1986: Dysmutagenic effect of cultured milk on chemically induced mutagenesis in escherichia coli b r wp 2 trp minus hcr minus. Dysmutagenic properties of milk cultured with Lactobacillus bulgaricus IFO3533, Streptococcus lactis IFO12546 or Str. faecalis IFO12964 against 4NQO and the water extract of dog feces were examined in vitro using the Escherichia coli B/r WP2 trp-...

Muday, G.K.; Peer, W.A.; Murphy, A.S.; Muday, G.K., 2003: Vesicular cycling mechanisms that control auxin transport polarity. The polar transport of auxin controls many important plant growth and developmental processes. The polarity of auxin movement has long been suggested to be mediated by asymmetric distribution of auxin transport proteins, yet, until recently, littl...

Masoro E.J.; Y.B.P.; Bertrand H.A., 1974: Calcium binding by rat sarcoplasmic reticulum membranes and by a water soluble protein fraction isolated from these membranes. Drabikowski, Witold, Hanna Strzeleck-Golaszewska And Ernesto Carafoli (Ed ) Calcium Binding Proteins Proceedings Of A Symposium Jablonna, Poland, July 9-12, 1973 Xx+945p Illus Pwn-Polish Scientific Publishers: Warsaw, Poland (Dist in U S And Canada By American Elsevier Publishing, Company, Inc , New York, N Y ) Isbn 0-444-99889-6 347-367

Resnik, L., 2013: Research and data systems to promote equal access to postacute rehabilitation. The first national study in Israel of post-acute rehabilitation service use for elderly patients with stroke and hip fracture reported regional variation in care receipt. Although lower likelihood of admission to inpatient rehabilitation was obser...

Rankin, G.O.; Yang, D.J.; Teets, V.J.; Lo, H.H.; Brown, P.I., 1986: 3,5-Dichloroaniline-induced nephrotoxicity in the Sprague-Dawley rat. The nephrotoxic potential of 3,5-dichloroaniline (DCA) was examined in male Sprague-Dawley rats. Rats were administered DCA (0.4, 0.8 or 1.0 mmol/kg, i.p.), or 0.9% saline (1.0 ml/kg, i.p.), and renal function was monitored at 24 and 48 h. DCA (0....

Kurth, A.; Weber, A.; Kranz, J., 1993: Studies on pest communities on ears of winter wheat (Triticum aestivum L.). Changes in pest communities (arthropods and fungi) on ears of winter wheat were studied at 5 growth stages from DC 51-85. Despite unfavourable weather conditions, the mean number of arthropod species present ranged from 2.7 (DC 51)-12.5 (DC 75) pe...

Asai, S.; Watanabe, T.; Sakamoto, J.; Kiriyama, K.; Ito, K.; Akiyama, S.; Takagi, H., 1994: Expression and prognostic indicators of type 1 and type 2 Lewis blood group antigens in colorectal cancers. The immunohistochemical analysis using the monoclonal antibodies to the blood group antigens was performed on the tissues of 387 colorectal cancers and 307 normal colonic tissues, and the relation between expression of these antigens and prognosis...

Wang, L-Qin.; He, Y.; Wan, H-Fang.; Zhou, H-Fen.; Yang, J-Hong.; Wan, H-Tong., 2017: Protective mechanisms of hypaconitine and glycyrrhetinic acid compatibility in oxygen and glucose deprivation injury. This study investigated the protective effect of the compatibility of hypaconitine (HA) and glycyrrhetinic acid (GA) on H9c2 cells under oxygen and glucose deprivation (OGD)-induced injury, and the possible mechanisms. We found that HA+GA signific...

Numo, R., 1992: Possible interaction between the infectious agents and the host in some rheumatic disorders. Balint, G [Editor], Gomor, B [Editor], Hodinka, L [Editor] International Congress Series; Rheumatology, state of the art : 259-262