Abstract
Since Protein A (PA) of Staphylococcus aureus has been documented to have both antitumor and immunostimulatory properties, we attempted to determine whether PA-induced tumor cell death was effected through the immune system of the host, and analyze the mechanisms of such anti-tumor activity. For in vivo studies, Ehrlich's ascites carcinoma (EAC) cells were inoculated into the peritoneal cavity of Swiss albino mice. PA (1 micro g/20 g body weight) was injected biweekly for 2 weeks. To determine the role of immunomodulators in PA-induced tumor cell death, EAC were co-cultured with PA-primed splenic cells or with the spent medium of the same. Our results indicated a "two-step" mechanism of the induction of apoptosis in tumor cells, by PA, i.e. (1) activation of the immune system of the host to release different apoptogenic factors like tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO); and (2) induction of EAC apoptosis by these soluble immune mediators through the up-regulation of pro-apoptotic factors (p53 and Bax) and down-regulation of anti-apoptotic factor (Bcl-2), resulting in the activation of caspase-3. The present observations provide additional findings on an approach to cancer immunotherapy that causes apoptogenic insult to cancer cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adjuvants, Immunologic / pharmacology*
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Adjuvants, Immunologic / therapeutic use
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Animals
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Apoptosis / drug effects*
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Apoptosis / physiology
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Carcinoma, Ehrlich Tumor / immunology
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Carcinoma, Ehrlich Tumor / pathology
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Carcinoma, Ehrlich Tumor / therapy*
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Caspase 3
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Caspases / biosynthesis
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Caspases / genetics
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Caspases / physiology*
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Culture Media, Conditioned / pharmacology
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Enzyme Induction / drug effects
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Gene Expression Regulation, Neoplastic / drug effects
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Genes, bcl-2
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Mice
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Neoplasm Proteins / biosynthesis
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Neoplasm Proteins / genetics
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Neoplasm Proteins / physiology
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Neoplasm Transplantation
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Nitric Oxide / physiology*
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Proto-Oncogene Proteins / biosynthesis
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / physiology*
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Proto-Oncogene Proteins c-bcl-2 / biosynthesis
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Proto-Oncogene Proteins c-bcl-2 / physiology*
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Staphylococcal Protein A / pharmacology*
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Staphylococcal Protein A / therapeutic use
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Tumor Cells, Cultured / drug effects
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Tumor Cells, Cultured / immunology
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Tumor Necrosis Factor-alpha / physiology*
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Tumor Suppressor Protein p53 / biosynthesis
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / physiology*
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bcl-2-Associated X Protein
Substances
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Adjuvants, Immunologic
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Bax protein, mouse
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Culture Media, Conditioned
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Neoplasm Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Staphylococcal Protein A
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Tumor Necrosis Factor-alpha
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Tumor Suppressor Protein p53
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bcl-2-Associated X Protein
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Nitric Oxide
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Casp3 protein, mouse
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Caspase 3
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Caspases