Avaliação da atividade antitumoral do monoterpeno Citronelal na linhagem celular de melanoma humano A2058
Data
2021-02-22
Autores
Dias, Sofia Munaro 
Orientadores
Machado Junior, Joel
Tipo
Trabalho de conclusão de curso
Título da Revista
ISSN da Revista
Título de Volume
Resumo
O melanoma é um tipo de câncer de pele que tem origem nos
melanócitos devido ao acúmulo de mutações em genes que regulam diferentes
etapas do processo tumorigênico como sobrevivência, proliferação, migração e
invasão. A terapia do melanoma baseia-se na ressecção cirúrgica do tumor,
radioterapia, quimioterapia ou imunoterapia. Diversos compostos derivados de
fontes naturais, como plantas, já são utilizados no tratamento contra o câncer.
Particularmente os terpenóides, que compreendem uma família de compostos
naturais com grande variedade química e estrutural devido à quantidade de
isoprenos na sua molécula, tem se mostrado efetivo no controle da proliferação
e sobrevivência celular em diferentes tipos de câncer, evidenciando seu
potencial como agente antitumoral. Entretanto, pouco se sabe sobre o efeito
desses compostos em tumores altamente metastáticos como melanomas que
apresentam mutações nos genes B-RAFV600E e PTEN, os quais conferem
resistência a terapias convencionais. Nesse sentido, o objetivo deste trabalho
foi avaliar o potencial antitumoral do monoterpeno Citronelal, extraído e
purificado a partir de constituintes do óleo essencial das folhas da espécie
vegetal Lippia Alba, na linhagem celular de melanoma humano A2058 que
apresenta mutações em B-RAFV600E e PTEN. Nossos resultados mostraram que
o Citronelal: 1) inibiu a viabilidade das células A2058 de forma concentração e
tempo dependente, avaliado por ensaios de MTT; 2) Induziu apoptose de forma
concentração dependente, avaliado por ensaios de anexina V; 3) inibiu a
capacidade de migração das células A2058 sugerindo um efeito inibitório em
uma etapa importante do processo metastático, avaliado por ensaios de wound
healing; 4) inibiu a atividade da quinase AKT, mas não da quinase ERK,
componentes de vias de sinalização que regulam sobrevivência, proliferação e
migração celular. Juntos nossos dados mostraram que o Citronelal apresenta
efeito inibitório in vitro na regulação de importantes eventos celulares, sugerindo
uma atividade antitumoral potencial em melanomas.
Melanoma is a type of skin cancer that originates in melanocytes due to the accumulation of mutations in genes that regulate cell survival, proliferation, migration and invasion. Melanoma therapy is based on surgical resection of the tumor, radiotherapy, chemotherapy or immunotherapy. Several compounds derived from natural sources, such as plants, are already used in the treatment against cancer. Particularly terpenoids, which comprise a family of natural compounds with large chemical and structural variety, have been shown to be effective in controlling cell proliferation and survival in different types of cancer, evidencing their potential as an antitumor agent. However, little is known about the effect of these compounds on highly metastatic tumors such as melanomas harboring mutations in B-RAFV600E and PTEN genes, which confer resistance to conventional therapies. In this regard, the objective of this work was to evaluate the potential anti-tumor effect of the monoterpene Citronellal, extracted and purified from the essential oil of the leaves of the Lippia Alba plant specie, using the human melanoma cell line A2058 (B-RAFV600E and PTEN mutation) as model. Our results showed that Citronellal: 1) inhibited the viability of A2058 cells in a concentration and time dependent manner, evaluated by MTT assays; 2) Induced apoptosis in a concentration dependent manner, evaluated by annexin V assays; 3) inhibited the migration capacity of A2058 cells suggesting an inhibitory effect in an important stage of the metastatic process; 4) inhibited AKT kinase activity, but not of ERK, components of signaling pathways that regulate survival, proliferation and migration. Together our data showed that Citronellal has an in vitro inhibitory effect on the regulation of important cellular events, suggesting a potential anti-tumor activity in melanomas.
Melanoma is a type of skin cancer that originates in melanocytes due to the accumulation of mutations in genes that regulate cell survival, proliferation, migration and invasion. Melanoma therapy is based on surgical resection of the tumor, radiotherapy, chemotherapy or immunotherapy. Several compounds derived from natural sources, such as plants, are already used in the treatment against cancer. Particularly terpenoids, which comprise a family of natural compounds with large chemical and structural variety, have been shown to be effective in controlling cell proliferation and survival in different types of cancer, evidencing their potential as an antitumor agent. However, little is known about the effect of these compounds on highly metastatic tumors such as melanomas harboring mutations in B-RAFV600E and PTEN genes, which confer resistance to conventional therapies. In this regard, the objective of this work was to evaluate the potential anti-tumor effect of the monoterpene Citronellal, extracted and purified from the essential oil of the leaves of the Lippia Alba plant specie, using the human melanoma cell line A2058 (B-RAFV600E and PTEN mutation) as model. Our results showed that Citronellal: 1) inhibited the viability of A2058 cells in a concentration and time dependent manner, evaluated by MTT assays; 2) Induced apoptosis in a concentration dependent manner, evaluated by annexin V assays; 3) inhibited the migration capacity of A2058 cells suggesting an inhibitory effect in an important stage of the metastatic process; 4) inhibited AKT kinase activity, but not of ERK, components of signaling pathways that regulate survival, proliferation and migration. Together our data showed that Citronellal has an in vitro inhibitory effect on the regulation of important cellular events, suggesting a potential anti-tumor activity in melanomas.