期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
卷 135, 期 -, 页码 261-273出版社
ELSEVIER
DOI: 10.1016/j.ijbiomac.2019.05.164
关键词
BthTX-II; EMT; Breast cancer; Phospholipase A(2)-snake venom
资金
- CAPES
- FAPEMIG [CBB - APQ-01401-17, CBB-APQ-01637-15]
- CNPq
- Federal University of Uberlandia (UFU), Brazil
- National Institute of Science and Technology in Theranostics and Nanobiotechnology INCT-TeraNano-CNPq/CAPES/FAPEMIG [CNPq-465669/2014-0]
- FAPEMIG
This work shows the antitumor and antimetastatic effects of BthTX-II, an Asp-49 PLA(2) from Bothrops jararacussu venom, on MDA-MB-231 human triple negative breast cancer cells. BthTX-II caused a dose-dependent cell death of MDA-MB-231 cells when compared with the non-tumorigenic breast cells by inducing apoptosis and autophagy. BthTX-II was also able to decrease the proliferation and to inhibit cell cycle progression. We also observed an upregulation of the ATM gene, which is responsible for cell-cycle arrest and DNA repair such as CCND1, CCNE1, CDC25A, E2F1, AKT1 and AKT3. Interestingly, BthTX-II inhibited invasion, migration and 3D cell growth of MDA-MB-231 cells, as well as inhibited the epithelial-mesenchymal transition (EMT) of this cell by increasing E-cadherin (CDH-1) and decreasing 111/15T1, CTNNB1, vimentin and cytokeratin-5 expression. In conclusion, these results showed that BthTX-ll displays antitumor and antimetastatic effects on MDA-MB-231 cells and may be useful for the development of new approaches and therapeutic strategies to manage triple negative breast cancer. (C) 2019 Published by Elsevier B.V.
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