Inhibitors epidermoid carcinoma

Akiyama T, Yoshida T, Tsujita T, Shimizu M, Mizukami T, Okabe M, Akinaga S (1997) G1 phase accumulation induced by UCN-01 is associated with dephosphorylation of Rb and CDK2 proteins as well as induction of CDK inhibitor p21/CiplAVAFl/Sdil in p53-mutated human epidermoid carcinoma A431 cells. Cancer Res 57 1495-1501... 

Culture filtrates of Streptomyces were screened for inhibitors of tyrosine kinase in the membrane fraction of human epidermoid carcinoma cell line A431. These cells contain a large number of EGF receptors with tyrosine kinase activity on their membrane. One strain was found to produce a novel compound that inhibited tyrosine kinase (Fig. 3). It was named erbstatin (1). Taxonomic studies indicated that the strain producing erbstatin is closely related to Streptomyces viridosporus. 

In vitro cytotoxicity of Ik and II was examined using L1210 and KB (human oral epidermoid carcinoma) cells. Compound Ik was inactive up to 100 pg/mL, while II was a potent inhibitor of growth of both cell lines with ICso s of 3.2 and 2.0 pgAnL, respectively. These differences might be a reflection of susceptibility to deoxycytidine kinase. Although the cytotoxicity of II was about 10 times less than that of CNDAC, we plan to compare its activity with other active nucleosides and examine its in vivo activity. 

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