Cytotoxic effect of wasp venom peptides in breast cancer cells

Detalhes bibliográficos
Autor(a) principal: Soares, Susana Isabel Nascimento
Data de Publicação: 2021
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10773/33578
Resumo: Currently, cancer is the second leading cause of death in the world and a clear threat to public health, leading to the death of almost 10 million people per year. Breast cancer, specifically, remains the most common cancer in women. Their complications and associated deaths highlight the need to develop new therapeutic agents to combat the disease. Venoms are mostly composed of an extensive and complex panoply of natural and biologically active chemical compounds, that are effective against various pathogenic microorganisms and some diseases, such as cancer. Several studies reported that a wide variety of viper, scorpion, and bee species produce venoms with compounds that have strong anti-tumor properties. However, some species in the Vespidae family are still poorly studied in terms of their antitumor potential, for example the social wasp species Polybia dimorpha and Chartergellus communis, which has no associated studies on this subject. Thus, in order to evaluate the antitumor potential of two new peptides from the social wasps P. dimorpha (Prolistarin) and C. communis (Chartergellus-CP1), assays were performed to determine their cytotoxicity against two breast cancer cell lines: the MCF-7 cell line and the MDA-MB-231 cell line. These lines were exposed to different concentrations of each peptide, for 24h and 48h, in order to evaluate their cell viability along time exposure. Prolistarin showed no relevant cytotoxicity against the studied cell lines. In contrast, the Chartergellus-CP1 peptide proved to be highly cytotoxic against both cell lines, promoting a high dose-dependent antitumor action. Thus, IC20 and IC50 of Chartergellus-CP1 were used to assess cell cycle dynamics, intracellular reactive oxygen species (ROS) production and apoptosis in both breast cancer cell lines. The results showed, for both cell lines, Chartergellus-CP1 leaded to a significant increase of cells in the S phase of the cell cycle, as well as to a high generation of ROS (being more evident in the MCF-7 cell line). We predict that this ROS production is associated with cell death in both cell lines, as both cells showed a significant increase of cells in early apoptosis when exposed to IC50. This dissertation demonstrated, for the first time, that the Chartergellus-CP1 peptide from the venom of Chartergellus communis wasps has high potential in breast cancer treatment.
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spelling Cytotoxic effect of wasp venom peptides in breast cancer cellsBreast cancerMCF-7MDA-MB-231Wasp venomPolybia dimorphaChartergellus communisAntitumor potentialCellular cytotoxicityProlistarinChartergellus-CP1Currently, cancer is the second leading cause of death in the world and a clear threat to public health, leading to the death of almost 10 million people per year. Breast cancer, specifically, remains the most common cancer in women. Their complications and associated deaths highlight the need to develop new therapeutic agents to combat the disease. Venoms are mostly composed of an extensive and complex panoply of natural and biologically active chemical compounds, that are effective against various pathogenic microorganisms and some diseases, such as cancer. Several studies reported that a wide variety of viper, scorpion, and bee species produce venoms with compounds that have strong anti-tumor properties. However, some species in the Vespidae family are still poorly studied in terms of their antitumor potential, for example the social wasp species Polybia dimorpha and Chartergellus communis, which has no associated studies on this subject. Thus, in order to evaluate the antitumor potential of two new peptides from the social wasps P. dimorpha (Prolistarin) and C. communis (Chartergellus-CP1), assays were performed to determine their cytotoxicity against two breast cancer cell lines: the MCF-7 cell line and the MDA-MB-231 cell line. These lines were exposed to different concentrations of each peptide, for 24h and 48h, in order to evaluate their cell viability along time exposure. Prolistarin showed no relevant cytotoxicity against the studied cell lines. In contrast, the Chartergellus-CP1 peptide proved to be highly cytotoxic against both cell lines, promoting a high dose-dependent antitumor action. Thus, IC20 and IC50 of Chartergellus-CP1 were used to assess cell cycle dynamics, intracellular reactive oxygen species (ROS) production and apoptosis in both breast cancer cell lines. The results showed, for both cell lines, Chartergellus-CP1 leaded to a significant increase of cells in the S phase of the cell cycle, as well as to a high generation of ROS (being more evident in the MCF-7 cell line). We predict that this ROS production is associated with cell death in both cell lines, as both cells showed a significant increase of cells in early apoptosis when exposed to IC50. This dissertation demonstrated, for the first time, that the Chartergellus-CP1 peptide from the venom of Chartergellus communis wasps has high potential in breast cancer treatment.Atualmente, o cancro é a segunda principal causa de morte no mundo e uma clara ameaça para a saúde pública, levando anualmente à morte de quase 10 milhões de pessoas. O cancro da mama, especificamente, continua a ser o mais frequente em mulheres tendo ainda muitas complicações e mortes associadas o que torna evidente a necessidade de desenvolver novos agentes terapêuticos para o combater. Os venenos são na sua maioria constituídos por uma panóplia extensa e complexa de compostos químicos naturais e biologicamente ativos, eficazes contra vários microrganismos patogénicos e algumas doenças, como o cancro. São vários os estudos que concluíram que diversas espécies de víboras, escorpiões e abelhas produzem venenos ricos em compostos com fortes propriedades antitumorais. No entanto, a família Vespidae está muito pouco estudada no que concerne ao seu potencial antitumoral, uma vez que existem muitas espécies por explorar, como é o caso da espécie de vespa social Polybia dimorfa e da Chartergellus communis. Assim, com o objetivo de avaliar o potencial antitumoral de dois novos péptidos provenientes do veneno das vespas sociais P.dimorpha (Prolistarina) e C. communis (Chartergellus-CP1), foram realizados ensaios para estudar a sua citotoxicidade em duas linhas celulares de cancro da mama: a linha celular MCF-7 e a linha celular MDA-MB-231. Estas células foram expostas a diferentes concentrações de cada péptido, durante 24h e 48h, de modo a avaliar a dose resposta através da análise da viabilidade celular ao longo do tempo de exposição. A Prolistarina não apresentou citotoxicidade relevante nas linhas celulares estudadas. Em contraste, o péptido Chartergellus-CP1 revelou-se altamente citotóxico contra ambas as linhas celulares, promovendo uma elevada diminuição da viabilidade com o aumento da concentração. Assim, foram calculados o IC20 e IC50 deste peptido e estudados os mecanismos de citotoxicidade nas duas linhas celulares, através da análise da dinâmica do ciclo celular, da produção intracelular de espécies reativas de oxigénio (ROS) e da apoptose. Os resultados mostraram que o Chartergellus-CP1 originou, em ambas as linhas celulares, um aumento significativo das células na fase S do ciclo celular assim como, um aumento de ROS (este mais evidente na linha celular MCF-7). Prevemos que esta produção de ROS esteja associada com a morte celular em ambas as linhas celulares, uma vez que as duas apresentaram um aumento significativo de células em apoptose inicial quando expostas ao IC50. Esta dissertação demostrou, pela primeira vez, que o péptido Chartergellus-CP1 do veneno da vespa Chartergellus communis tem um elevado potencial biotecnológico no combate ao cancro da mama.2023-12-22T00:00:00Z2021-12-16T00:00:00Z2021-12-16info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10773/33578engSoares, Susana Isabel Nascimentoinfo:eu-repo/semantics/embargoedAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-02-22T12:04:39Zoai:ria.ua.pt:10773/33578Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:04:59.749464Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Cytotoxic effect of wasp venom peptides in breast cancer cells
title Cytotoxic effect of wasp venom peptides in breast cancer cells
spellingShingle Cytotoxic effect of wasp venom peptides in breast cancer cells
Soares, Susana Isabel Nascimento
Breast cancer
MCF-7
MDA-MB-231
Wasp venom
Polybia dimorpha
Chartergellus communis
Antitumor potential
Cellular cytotoxicity
Prolistarin
Chartergellus-CP1
title_short Cytotoxic effect of wasp venom peptides in breast cancer cells
title_full Cytotoxic effect of wasp venom peptides in breast cancer cells
title_fullStr Cytotoxic effect of wasp venom peptides in breast cancer cells
title_full_unstemmed Cytotoxic effect of wasp venom peptides in breast cancer cells
title_sort Cytotoxic effect of wasp venom peptides in breast cancer cells
author Soares, Susana Isabel Nascimento
author_facet Soares, Susana Isabel Nascimento
author_role author
dc.contributor.author.fl_str_mv Soares, Susana Isabel Nascimento
dc.subject.por.fl_str_mv Breast cancer
MCF-7
MDA-MB-231
Wasp venom
Polybia dimorpha
Chartergellus communis
Antitumor potential
Cellular cytotoxicity
Prolistarin
Chartergellus-CP1
topic Breast cancer
MCF-7
MDA-MB-231
Wasp venom
Polybia dimorpha
Chartergellus communis
Antitumor potential
Cellular cytotoxicity
Prolistarin
Chartergellus-CP1
description Currently, cancer is the second leading cause of death in the world and a clear threat to public health, leading to the death of almost 10 million people per year. Breast cancer, specifically, remains the most common cancer in women. Their complications and associated deaths highlight the need to develop new therapeutic agents to combat the disease. Venoms are mostly composed of an extensive and complex panoply of natural and biologically active chemical compounds, that are effective against various pathogenic microorganisms and some diseases, such as cancer. Several studies reported that a wide variety of viper, scorpion, and bee species produce venoms with compounds that have strong anti-tumor properties. However, some species in the Vespidae family are still poorly studied in terms of their antitumor potential, for example the social wasp species Polybia dimorpha and Chartergellus communis, which has no associated studies on this subject. Thus, in order to evaluate the antitumor potential of two new peptides from the social wasps P. dimorpha (Prolistarin) and C. communis (Chartergellus-CP1), assays were performed to determine their cytotoxicity against two breast cancer cell lines: the MCF-7 cell line and the MDA-MB-231 cell line. These lines were exposed to different concentrations of each peptide, for 24h and 48h, in order to evaluate their cell viability along time exposure. Prolistarin showed no relevant cytotoxicity against the studied cell lines. In contrast, the Chartergellus-CP1 peptide proved to be highly cytotoxic against both cell lines, promoting a high dose-dependent antitumor action. Thus, IC20 and IC50 of Chartergellus-CP1 were used to assess cell cycle dynamics, intracellular reactive oxygen species (ROS) production and apoptosis in both breast cancer cell lines. The results showed, for both cell lines, Chartergellus-CP1 leaded to a significant increase of cells in the S phase of the cell cycle, as well as to a high generation of ROS (being more evident in the MCF-7 cell line). We predict that this ROS production is associated with cell death in both cell lines, as both cells showed a significant increase of cells in early apoptosis when exposed to IC50. This dissertation demonstrated, for the first time, that the Chartergellus-CP1 peptide from the venom of Chartergellus communis wasps has high potential in breast cancer treatment.
publishDate 2021
dc.date.none.fl_str_mv 2021-12-16T00:00:00Z
2021-12-16
2023-12-22T00:00:00Z
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