Antitumor effects in vitro and in vivo and mechanisms of protection against melanoma B16F10-Nex2 cells by fastuosain, a cysteine proteinase from Bromelia fastuosa.
In the present work, the antitumor effect of fastuosain, a cysteine proteinase from Bromelia fastuosa, was investigated. In the intravenous model of lung colonization in C57Bl/6 mice, fastuosain and bromelain injected intraperitoneally were protective, and very few nodules of B16F10-Nex2 melanoma cells were detected. Tumor cells treated with fastuosain showed reduced expression of CD44 and decreased invasion through Matrigel, lost their cytoplasmic extensions and substrate adherence, and became round and detached, forming strongly bound cell clusters in suspension. Peritoneal cells recruited and activated by fastuosain treatment (mainly monocytic cells and lymphocytes) migrated to the lung, where pulmonary melanoma metastases grew. Adoptive transference of peritoneal cells recruited by fastuosain had no protective effect against lung metastases in recipient mice. Treatment of green fluorescent protein-chimeric animals with fastuosain did not change the number of cells that migrated to the lung, compared to PBS-injected control mice, but the number of positive major histocompatibility complex class II cells increased with fastuosain treatment. Murine antibodies against fastuosain, bromelain, and cathepsins B and L cross-reacted in ELISA and recognized surface and cytoplasmic components expressed on B16F10-Nex2 cells. Anti-fastuosain antibodies were cytotoxic/lytic to B16F10-Nex2 cells. Antitumor effects of fastuosain involve mainly the direct effect of the enzyme and elicitation of protective antibodies.
Guimarães-Ferreira
Carla A
CA
Experimental Oncology Unit, Department of Microbiology, Immunology, and Parasitology, Federal University of São Paulo, São Paulo, Brazil.
Rodrigues
Elaine G
EG
Mortara
Renato A
RA
Cabral
Hamilton
H
Serrano
Fabiana A
FA
Ribeiro-dos-Santos
Ricardo
R
Travassos
Luiz R
LR
D019264:Adoptive Transfer; D000818:Animals; D000917:Antibody Formation; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000276:immunology; D000972:Antineoplastic Agents, Phytogenic / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D001963:Bromelains / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003546:Cysteine Endopeptidases / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D004354:Drug Screening Assays, Antitumor; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000556:secondary*; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000637:transplantation; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010206:Papain / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D011828:Radiation Chimera
D000951:Antigens, Neoplasm; D000972:Antineoplastic Agents, Phytogenic; D001963:Bromelains; D003546:Cysteine Endopeptidases; C509400:fastuosain, Bromelia fastuosa; D010206:Papain