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| Titel: |
Oridonin induces human melanoma A375-S2 cell death partially through inhibiting insulin-like growth factor 1 receptor signaling |
| Auteur: |
Wang, Hong-Jun Li, Dan Yang, Fan-Yi Tashiro, Shin-ichi Onodera, Satoshi Ikejima, Takashi |
| Verschenen in: |
Journal of Asian natural products research |
| Paginering: | Jaargang 10 (2008) nr. 8 pagina's 777-788 |
| Jaar: |
2008-08 |
| Inhoud: |
Our previous studies indicated that oridonin, a diterpenoid isolated from Rabdosia rubescens, induced human melanoma A375-S2 cell apoptosis. In this study, we investigated whether the proapoptotic effect of oridonin on A375-S2 cells would depend on an interference with function of the insulin-like growth factor 1 (IGF-1) receptor, a plasma membrane receptor critical for the survival or antiapoptotic ability in melanoma cells. We found that IGF-1 receptor (IGF-1R) signaling was a potential survival pathway against a low concentration of 20 μmol/L oridonin-induced apoptosis in A375-S2 cells. The activation of Ras or its downstream effector p38 mitogen-activated protein kinase (p38 MAPK) was shown to be necessary for IGF-1-mediated protection, but the activation of phosphatidylinositol-3-OH kinase (PI3 kinase) or extracellular signal-regulated kinase (ERK) did not correlate with the regulation of survival. However, in the presence of 40 μmol/L (IC50 at 24 h) oridonin, A375-S2 cells could not be protected by IGF-1 from apoptosis, accompanied by a severe impairment of IGF-1R expression. Therefore, we concluded that the proapoptotic activity of oridonin was partially attributed to its repression of IGF-1R signaling. In addition, p53 was supposed to be a pivotal transducer of proapoptotic and survival signaling pathway in this system. |
| Uitgever: |
Taylor & Francis |
| Bronbestand: |
Elektronische Wetenschappelijke Tijdschriften |
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