BthTX-I from Bothrops jararacussu induces apoptosis in human breast cancer cell lines and decreases cancer stem cell subpopulation

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07/29/2019

Patrícia Heloise Alves Bezerra, Isadora Marques Ferreira, Beatriz Tinoco Franceschi, Francine Bianchini, Luciana Ambrósio, Adélia Cristina O. Cintra, Suely Vilela Sampaio, Fabíola Attié de Castro, Maria Regina Torqueti

Journal of Venomous Animals and Toxins including Tropical Diseases 2019;25:2019-0010
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1678-91992019000100315&lng=en&nrm=iso&tlng=en | © The Author(s). 2019
Received: February 22, 2019 | Accepted: June 04, 2019 | Published: July 29, 2019

ABSTRACT

Background

Breast cancer is the neoplasm with both the highest incidence and mortality rate among women worldwide. Given the known snake venom cytotoxicity towards several tumor types, we evaluated the effects of BthTX-I from Bothrops jararacussu on MCF7, SKBR3, and MDAMB231 breast cancer cell lines.

Methods

BthTX-I cytotoxicity was determined via MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide assay. Cell death was measured by a hypotonic fluorescent solution method, annexin-V-FITC/propidium iodide staining and by apoptotic/autophagic protein expression. Cancer stem cells (CSCs) were quantified by flow cytometry using anti-CD24-FITC and anti-CD44-APC antibodies and propidium iodide.

Results

BthTX-I at 102 µg/mL induced cell death in all cell lines. The toxin induced apoptosis in MCF7, SKBR3, and MDAMB231 in a dose-dependent manner, as confirmed by the increasing number of hypodiploid nuclei. Expression of pro-caspase 3, pro-caspase 8 and Beclin-1 proteins were increased, while the level of the antiapoptotic protein Bcl-2 was diminished in MCF7 cells. BthTX-I changed the staining pattern of CSCs in MDAMB231 cells by increasing expression of CD24 receptors, which mediated cell death.

Conclusions

BthTX-I induces apoptosis and autophagy in all breast cancer cell lines tested and also reduces CSCs subpopulation, which makes it a promising therapeutic alternative for breast cancer.

PubMed Central https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6665320/

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KEYWORDS

apoptosis
bothropstoxin
breast cancer
cancer stem cells
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