Growth suppression of low HER-2/neu-expressing breast cancer cell line MDA-MB-435 by tyrosine kinase inhibitor emodin.

The tyrosine kinase inhibitor emodin (3-methyl-1,6,8-tridroxyanthaquinone) is known to preferentially suppress the growth of the HER-2/neu-overexpressing breast cancer cell line. In this study, emodin effectively suppressed growth of MDA-MB-435, a breast cancer cell line with low HER-2/neu expression. Since emodin is a tyrosine kinase inhibitor, we questioned whether another tyrosine kinase might play a role in the tumorigenicity of MDA-MB-435. By Western blotting with anti-phosphotyrosine antibody, we detected a 72-kDa protein which is uniquely phosphorylated on tyrosine in MDA-MB-435. The level of phosphotyrosine in the 72-kDa protein was significantly reduced by treatment with emodin. This suggests that a strong tyrosine kinase may reside in MDA-MB-435 and the 72-kDa protein serves as a substrate for the tyrosine kinase.