Abstract
We studied the mechanism of anti-tumour action of sulphydryl glycoprotein (SAGP) purified from an extract of Streptococcus pyogenes in vitro. SAGP rapidly inhibited the incorporation of nucleic acid precursors into murine fibrosarcoma (Meth A) cells before it inhibited the cell growth. SAGP-induced cell growth inhibition was diminished by incubating the cells with pertussis toxin (IAP), whereas the SAGP activity was augmented by incubating the cells with cholera toxin (CTX). Meth A cells exposed to SAGP underwent an increase in labelling of the alpha-subunit of an inhibitory guanine nucleotide-binding (Gi) protein in a subsequent IAP-catalysed [32P]ADP ribosylation of the cell membrane fraction. Gi alpha labelling was not increased either in the membrane from the Meth A cells exposed to heat-inactivated SAGP or in the membrane from L929 cells exposed to SAGP, in which growth was also unaffected. By contrast, SAGP caused no alteration in labelling the alpha-subunit of stimulatory guanine nucleotide-binding (Gs) protein in a subsequent CTX-catalysed ADP ribosylation of membrane fractions of Meth A and L929 cells. The amount of intracellular cAMP was decreased slightly in Meth A cells incubated with SAGP. Although the precise roles of Gs protein and adenylate cyclase in the cell growth inhibition induced by SAGP are not clear, these findings suggested that the modulation of Gi protein is involved in such SAGP-induced cellular events as the inhibition of nucleic acid synthesis and cell growth inhibition.
Highlights
In the late 1800s, William B Coley and his colleagues described the cancer therapeutic effects of erysipelas-inducing streptococci (Nauts et al, 1946; Rook, 1992; Starnes, 1992)
We found that the antitumour activity of SAGP on Meth A cell line (Meth A) cells was modified by first exposing the cells to a bacterial toxin, pertussis toxin (IAP) or cholera toxin (CTX)
We showed previously that SAGP inhibits the growth of Meth A cells in vitro in a concentration-dependent manner (Yoshida et al, 1991)
Summary
In the late 1800s, William B Coley and his colleagues described the cancer therapeutic effects of erysipelas-inducing streptococci (Nauts et al, 1946; Rook, 1992; Starnes, 1992). We identified an acidic glycoprotein (SAGP) as having anti-tumour properties, from the Streptococcus pyogenes, Su strain (Yoshida et al, 1985). SAGP prolonged the life span of mice inoculated with Ehrlich ascites carcinoma cells or Meth A cells. As this effect of SAGP on the mice inoculated with these tumour cells was reduced when they were immunosuppressed by X-irradiation or with carrageenan, an anti-macrophage agent, hostmediated mechanisms were thought to be involved partly in the anti-tumour action of SAGP (Yoshida et al, 1991). The studies on the SAGP-induced cell growth inhibition using thiol reactive agents suggested that SH groups on SAGP are involved in the anti-tumour action of
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