Inhibition of growth of subcutaneous xenografts and metastasis of human breast carcinoma by swainsonine: modulation of tumor cell HLA class I antigens and host immune effector mechanisms.
Swainsonine, an indolizidine alkaloid, can decrease the organ colonization potential of metastatic murine tumor cells by augmentation of host immune effector mechanisms. In this report the above findings were extended by the demonstration that systemic administration of swainsonine strongly suppressed the growth of human breast carcinoma subcutaneous xenografts and experimentally induced lung metastases. This inhibition was not due to a direct effect of swainsonine on cell growth. However swainsonine treatment of tumor cells resulted in enhanced expression of HLA Class I antigens, and HLA class I mRNA. Swainsonine was a potent immunodulator as evidenced by the increased (a) cytotoxicity of splenocytes and macrophages, and, (b) proliferative potential of splenocytes and bone marrow cells. These data suggest that swainsonine-induced inhibition of tumor growth and metastases may be mediated via activation of host effector cells and/or alteration of tumor cell antigenicity.
Mohla
S
S
Howard University Cancer Center, Washington, D.C.
White
S
S
Grzegorzewski
K
K
Nielsen
D
D
Dunston
G
G
Dickson
L
L
Cha
J K
JK
Asseffa
A
A
Olden
K
K
D000470:Alkaloids / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D003602:Cytotoxicity, Immunologic; D015342:DNA Probes; D005260:Female; D005805:Genes, MHC Class I / Q000187:drug effects*; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000556:secondary*; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000276:immunology; D008361:Mannosidases / Q000037:antagonists & inhibitors; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D017026:Swainsonine; D014183:Transplantation, Heterologous
D000470:Alkaloids; D000970:Antineoplastic Agents; D015342:DNA Probes; D015395:Histocompatibility Antigens Class I; D012334:RNA, Neoplasm; D008361:Mannosidases; D017026:Swainsonine