Protein A-induced apoptosis of cancer cells is effected by soluble immune mediators.
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.
Animal Physiology Section, Bose Institute, P-1/12 CIT Scheme VII M, Kolkata-700054, India. tanya@boseinst.ernet.in
Tanya
T
Das
Gaurisankar
G
Sa
Sreya
S
Chattopadhyay
Prasanta K
PK
Ray
D000276:Adjuvants, Immunologic / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002286:Carcinoma, Ehrlich Tumor / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019254:Genes, bcl-2; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D009368:Neoplasm Transplantation; D009569:Nitric Oxide / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000502:physiology*; D013205:Staphylococcal Protein A / Q000494:pharmacology* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051028:bcl-2-Associated X Protein
D000276:Adjuvants, Immunologic; C494827:Bax protein, mouse; D017077:Culture Media, Conditioned; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D013205:Staphylococcal Protein A; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D009569:Nitric Oxide; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases