A new tick Kunitz type inhibitor, Amblyomin-X, induces tumor cell death by modulating genes related to the cell cycle and targeting the ubiquitin-proteasome system.
The aim of this study was to evaluate the anti-tumor activity of Amblyomin-X, a serine protease Kunitz-type inhibitor. Amblyomin-X induced tumor mass regression and decreased number of metastatic events in a B16F10 murine melanoma model. Alterations on expression of several genes related to cell cycle were observed when two tumor cell lines were treated with Amblyomin-X. PSMB2, which encodes a proteasome subunit, was differentially expressed, in agreement to inhibition of proteasomal activity in both cell lines. In conclusion, our results indicate that Amblyomin-X selectively acts on tumor cells by inducing apoptotic cell death, possibly by targeting the ubiquitin-proteasome system.
Chudzinski-Tavassi
Ana Marisa
AM
Laboratório de Bioquímica e Biofísica, Instituto Butantan, Av. Vital Brazil 1500, 05503-900, São Paulo SP, Brazil. amchudzinski@butantan.gov.br
De-Sá-Júnior
Paulo Luis
PL
Simons
Simone Michaela
SM
Maria
Durvanei Augusto
DA
de Souza Ventura
Janaina
J
Batista
Isabel de Fátima Correia
IF
Faria
Fernanda
F
Durães
Esther
E
Reis
Eduardo Moraes
EM
Demasi
Marilene
M
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D060829:Arthropod Proteins; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D026863:Ixodidae / Q000737:chemistry* / Q000235:genetics; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects / Q000378:metabolism*; D012469:Salivary Glands / Q000737:chemistry; D012471:Salivary Proteins and Peptides / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D025801:Ubiquitin / Q000378:metabolism*
C559369:Amblyomin-X protein, Amblyomma cajennense; D000970:Antineoplastic Agents; D060829:Arthropod Proteins; D012471:Salivary Proteins and Peptides; D015842:Serine Proteinase Inhibitors; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex