Bothrops Jararaca Snake Venom Modulates Key Cancer-Related Proteins in Breast Tumor Cell Lines

Author(s)

Kisaki, Carolina Yukiko ^{[1, 2]} ; Arcos, Stephanie Santos Suehiro ^{[1, 2]} ; Montoni, Fabio ^{[1, 2]} ; da Silva Santos, Wellington ^{[1, 2]} ; Calacina, Hamida Macedo ^{[1, 2]} ; Lima, Ismael Feitosa ^{[1, 2]} ; Cajado-Carvalho, Daniela ^{[1, 2]} ; Ferro, Emer Suavinho ^[3] ; Nishiyama-Jr, Milton Yutaka ; Iwai, Leo Kei ^{[4, 5]}

Affiliation

^[1] Butantan Inst, Lab Appl Toxinol LETA, BR-05503900 Sao Paulo - Brazil

^[2] Butantan Inst, Ctr Toxins Immune Response & Cell Signaling CeTIC, BR-05503900 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Biomed Sci Inst ICB, Dept Pharmacol, BR-05508000 Sao Paulo - Brazil

^[4] Nishiyama-Jr, Jr., Milton Yutaka, Butantan Inst, Lab Appl Toxinol LETA, BR-05503900 Sao Paulo - Brazil

^[5] Nishiyama-Jr, Jr., Milton Yutaka, Butantan Inst, Ctr Toxins Immune Response & Cell Signaling CeTIC, BR-05503900 Sao Paulo - Brazil

• Document type: Journal article
• Source: TOXINS; v. 13, n. 8 AUG 2021.
• Web of Science Citations: 0

Abstract

Cancer is characterized by the development of abnormal cells that divide in an uncontrolled way and may spread into other tissues where they may infiltrate and destroy normal body tissue. Several previous reports have described biochemical anti-tumorigenic properties of crude snake venom or its components, including their capability of inhibiting cell proliferation and promoting cell death. However, to the best of our knowledge, there is no work describing cancer cell proteomic changes following treatment with snake venoms. In this work we describe the quantitative changes in proteomics of MCF7 and MDA-MB-231 breast tumor cell lines following treatment with Bothrops jararaca snake venom, as well as the functional implications of the proteomic changes. Cell lines were treated with sub-toxic doses at either 0.63 mu g/mL (low) or 2.5 mu g/mL (high) of B. jararaca venom for 24 h, conditions that cause no cell death per se. Proteomics analysis was conducted on a nano-scale liquid chromatography coupled on-line with mass spectrometry (nLC-MS/MS). More than 1000 proteins were identified and evaluated from each cell line treated with either the low or high dose of the snake venom. Protein profiling upon venom treatment showed differential expression of several proteins related to cancer cell metabolism, immune response, and inflammation. Among the identified proteins we highlight histone H3, SNX3, HEL-S-156an, MTCH2, RPS, MCC2, IGF2BP1, and GSTM3. These data suggest that sub-toxic doses of B. jararaca venom have potential to modulate cancer-development related protein targets in cancer cells. This work illustrates a novel biochemical strategy to identify therapeutic targets against cancer cell growth and survival. (AU)

• FAPESP's process: 17/06496-9 - Proteomic characterization of the effect of Bothrops jararaca snake venom on normal vs cancer cell lines
• Grantee: Carolina Yukiko Kisaki
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling
• Grantee: Hugo Aguirre Armelin
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 16/04000-3 - Pharmacology of oligopeptidases and intracellular peptides
• Grantee: Emer Suavinho Ferro
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/17943-6 - Proteomic and peptidomic analysis of snake venom effect on cancer cell lines and mouse brain tissues
• Grantee: Leo Kei Iwai
• Support Opportunities: Regular Research Grants