Antiproliferative and apoptosis-inducing effects of an antitumor glycoprotein from Streptococcus pyogenes

An acidic glycoprotein (SAGP) purified from an extract of Streptococcus pyogenes has been shown to inhibit the growth of methylcholanthrene-induced fibrosarcoma A (Meth A) cells via pertussis toxin-sensitive GTP-binding protein. The present study revealed that SAGP has activity to induce apoptosis in Meth A cells as assessed by DNA fragmentation and cell morphology with chromatin staining. The SAGP-induced DNA fragmentation in Meth A cells was augmented by herbimycin A, an inhibitor of protein tyrosine kinase, and prevented by orthovanadate, an inhibitor of protein tyrosine phosphatase. The growth inhibitory effect of SAGP on Meth A cells was reduced by orthovanadate, whereas the effect tended to be increased by herbimycin A. Western blotting analysis using antiphosphotyrosine antibody demonstrated that tyrosine phosphorylation of 170 kDa cellular protein was diminished in the cells incubated with SAGP. The inhibition of protein tyrosine phosphorylation was neither observed in the cells incubated with SAGP and orthovanadate nor in the cells incubated with heat-inactivated SAGP. These findings indicate that inhibition of tyrosine phosphorylation by protein tyrosine phosphatase(s) may be responsible for the SAGP-induced apoptosis and inhibition of cell growth.