Publicação
Eucalyptus nitens antitumoral activity: a biochemical approach to assess the redox cellular state on tumor and non-tumor breast cells
| Resumo: | Cancer incidence is increasing worldwide and it is estimated that, by 2030, the number of new cases will be 22.2 milllion. The most common cancer among women is breast cancer and, in particularly, triple negative breast cancer (no ER, PR and HER2 expression) has poor prognosis. New emerging therapies are being developed but chemotherapy is still the standard treatment, having low effiency and with associated toxicity to normal tissues. Eucalyptus nitens can be a source of natural compounds with anticancer and antioxidant activities, namely ursolic (UA) and betulinic (BA) acids. Studies with these triterpenoids showed their capacity to induce cell death and inhibit proliferation in breast cancer cells with low toxicity in normal cells. In the present study, the ability E. nitens outer bark extract, UA, BA, and the combination of both (UB), to induce cell death in human breast cancer cells (MDA-MB-231) were tested. For that, the effect of these treatments on tumor and non-tumor breast cells was evaluated with resazurin, MTT, trypan bue and acridine orange and propidium iodide double staining. Our data showed higher cytotoxicity in MDA-MB-231 cells when treated with E. nitens outer bark extract, UA and BA. However, the combination of pure acids had contradictory results. The effect of triterpenoids acids in intracellular ROS levels was tested by DCF-DA assay but the results were inconclusive. In this study, we also analyzed different experimental approaches on the capability of forming spheroids using MCF-10A and MDA-MB- 231 cell lines. The distinct spheroid formation capabilities of different cell lines stress the need for standardization of spheroid generation protocols for better testing of novel anticancer drugs. Interestingly, it was possible to observe that incubation with E. nitens outer bark extract strongly affected spheroid integrity. Overall, the results suggest that E. nitens outer bark extract is a potential natural source of bioactive compounds for the development of chemopreventive agents, to inhibit or slow down the progression of breast cancer, although the mechanisms are yet to be fully elucidated. |
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| Autores principais: | Ferreira, Ana Sofia Mendes |
| Assunto: | Betulinic acid Breast cancer Eucalyptus nitens outer bark extract Spheroids Ursolic acid Ácido betulínico Ácido ursólico Cancro da mama Esferóides Extrato da casca externa de Eucalyptus nitens |
| Ano: | 2020 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| Resumo: | Cancer incidence is increasing worldwide and it is estimated that, by 2030, the number of new cases will be 22.2 milllion. The most common cancer among women is breast cancer and, in particularly, triple negative breast cancer (no ER, PR and HER2 expression) has poor prognosis. New emerging therapies are being developed but chemotherapy is still the standard treatment, having low effiency and with associated toxicity to normal tissues. Eucalyptus nitens can be a source of natural compounds with anticancer and antioxidant activities, namely ursolic (UA) and betulinic (BA) acids. Studies with these triterpenoids showed their capacity to induce cell death and inhibit proliferation in breast cancer cells with low toxicity in normal cells. In the present study, the ability E. nitens outer bark extract, UA, BA, and the combination of both (UB), to induce cell death in human breast cancer cells (MDA-MB-231) were tested. For that, the effect of these treatments on tumor and non-tumor breast cells was evaluated with resazurin, MTT, trypan bue and acridine orange and propidium iodide double staining. Our data showed higher cytotoxicity in MDA-MB-231 cells when treated with E. nitens outer bark extract, UA and BA. However, the combination of pure acids had contradictory results. The effect of triterpenoids acids in intracellular ROS levels was tested by DCF-DA assay but the results were inconclusive. In this study, we also analyzed different experimental approaches on the capability of forming spheroids using MCF-10A and MDA-MB- 231 cell lines. The distinct spheroid formation capabilities of different cell lines stress the need for standardization of spheroid generation protocols for better testing of novel anticancer drugs. Interestingly, it was possible to observe that incubation with E. nitens outer bark extract strongly affected spheroid integrity. Overall, the results suggest that E. nitens outer bark extract is a potential natural source of bioactive compounds for the development of chemopreventive agents, to inhibit or slow down the progression of breast cancer, although the mechanisms are yet to be fully elucidated. |
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