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Reduced antitumor and immune-adjuvant activities of the sub-cellular fractions from Group A Streptococcus
Abstract:
The sub-cellular fractions from Group A streptococcus (Su-strain) were prepared, and their antitumor and biological activities were examined. The cell wall fraction (CWF) and the protoplast membrane fraction (PMF) were slightly effective in retarding the growth of Ehrlich ascites carcinoma in outbred ddY mice when either fraction was used in combination with 5-FU. The cytoplasmic particle fraction (CPF) and the cytoplasmic soluble fraction (CSF), however, were not effective. In the B6D2F1 mice-L 1210 leukemia system, none of the subcellular fractions were beneficial even when combined with 5-FU. Further, the antitumor effect of OK-432 was completely abolished by disruption of the preparation, indicating that antitumor activity of OK-432 may depend on the structural integrity of the cocci in the preparation. Despite the general lack of anti-tumor activity in the mouse systems, the subcellular fractions, including those of OK-432, inhibited the growth of Yoshida sarcoma cells in culture and the uptake of [2H]-UR and [3H]-TdR by L 1210 cells in vitro. The immunopotentiating activities of these fractions, however, were demonstrated to be markedly diminished as compared with those of OK-432 and heated Su-cocci (60 degrees C, 30 min). The present study, therefore, shows that the decreased antitumor activity of the subcellular fractions closely correlate to the decrease of their immunopotentiating activities.
Insights
Subcellular fractions from Group A Streptococcus showed limited antitumor effects in mouse models. However, these fractions inhibited tumor cell growth in vitro, though with reduced immunopotentiating activity compared to the whole bacteria.
Area of Science:
- Immunology
- Microbiology
- Cancer Research
Background:
- Group A Streptococcus (Su-strain) and OK-432 are known for potential antitumor and immunomodulatory effects.
- Understanding the contribution of subcellular components to these activities is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the antitumor and biological activities of subcellular fractions from Group A Streptococcus (Su-strain).
- To determine the role of structural integrity in the antitumor activity of preparations like OK-432.
Main Methods:
- Preparation and isolation of subcellular fractions: cell wall (CWF), protoplast membrane (PMF), cytoplasmic particle (CPF), and cytoplasmic soluble (CSF).
- In vivo studies using Ehrlich ascites carcinoma and L 1210 leukemia mouse models, with and without 5-fluorouracil (5-FU).
- In vitro studies assessing inhibition of Yoshida sarcoma cell growth and nucleotide uptake ([3H]-UR, [3H]-TdR) by L 1210 cells.
- Evaluation of immunopotentiating activities of fractions compared to whole bacteria and OK-432.
Main Results:
- CWF and PMF showed slight retardation of Ehrlich ascites carcinoma growth in mice when combined with 5-FU; CPF and CSF were ineffective.
- No significant antitumor benefits were observed in the L 1210 leukemia mouse model, even with 5-FU.
- Antitumor activity of OK-432 was lost upon disruption, suggesting dependence on structural integrity.
- Subcellular fractions inhibited tumor cell growth and nucleotide uptake in vitro.
- Immunopotentiating activities of fractions were significantly diminished compared to intact Su-cocci and OK-432.
Conclusions:
- Decreased antitumor activity of subcellular fractions correlates with reduced immunopotentiating capacity.
- The structural integrity of Group A Streptococcus appears critical for its in vivo antitumor efficacy.