Stimulation of ultraviolet‐induced apoptosis of human fibroblast UVr‐1 cells by tyrosine kinase inhibitors

FEBS Letters

Kita, Kazuko²  Ito, Hisao³  Suzuki, Nobuo²  Chen, Zheng²  Arase, Yoshiko³  Umezawa, Kazuo¹  Hiwasa, Takaki² 

[1] Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-0061, Japan;Department of Biochemistry, School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8670, Japan;Department of Radiology, School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8670, Japan

关键词: Ultraviolet;    Tyrosine kinase inhibitor;    Mitogen-associated protein kinase;    Apoptosis;    Dam;    damnacanthal (3-hydroxy-1-methoxyanthraquinone-2-aldehyde);    DMSO;    dimethylsulfoxide;    ERK;    extracellular signal-regulated kinase;    HMA;    herbimycin A;    IC50;    half maximum inhibition concentration;    SAPK;    stress-activated protein kinase;    UV;    ultraviolet;   

DOI  :  10.1016/S0014-5793(99)00057-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Damnacanthal is an anthraquinone compound isolated from the root of Morinda citrifolia and was reported to have a potent inhibitory activity towards tyrosine kinases such as Lck, Src, Lyn and EGF receptor. In the present study, we have examined the effects of damnacanthal on ultraviolet ray-induced apoptosis in ultraviolet-resistant human UV^r-1 cells. When the cells were treated with damnacanthal prior to ultraviolet irradiation, DNA fragmentation was more pronounced as compared to the case of ultraviolet irradiation alone. The other tyrosine kinase inhibitors, herbimycin A and genistein, also caused similar effects on ultraviolet-induced apoptosis but to a lesser extent. Serine/threonine kinase inhibitors, K252a, staurosporine and GF109203X, rather suppressed the ultraviolet-induced DNA cleavage. Immunoblot analysis showed that pretreatment with damnacanthal followed by ultraviolet irradiation increased the levels of phosphorylated extracellular signal-regulated kinases and stress-activated protein kinases. However, the other tyrosine kinase inhibitors did not increase the phosphorylation of extracellular signal-regulated kinases but stimulated phosphorylation of stress-activated protein kinases. Consequently, the ultraviolet-induced concurrent increase in both phosphorylated extracellular signal-regulated kinases and stress-activated protein kinases after pretreatment with damnacanthal might be characteristically related to the stimulatory effect of damnacanthal on ultraviolet-induced apoptosis.

【 授权许可】

Unknown