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| Author(s): |
Paula Araujo Monteiro
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia |
| Defense date: | 2017-03-31 |
| Examining board members: |
João Ernesto de Carvalho;
Cristina Pontes Vicente;
Humberto Moreira Spindola;
Denise Gonçalves Priolli;
Taize Machado Augusto
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| Advisor: | Débora Barbosa Vendramini Costa; Mary Ann Foglio; João Ernesto de Carvalho |
| Abstract | |
The increase in life expectancy and habits that involve the exposure to carcinogens can promote the incidence of cancer, since aging and the chronic inflammation caused by many of these factors favor the development of tumors. Chemotherapy is the main strategy used in cancer treatment and in this context, most of the chemotherapies currently used are obtained from natural sources. Therefore, the aim of this work was to evaluate the composition of active fractions obtained from "Croton campestris" A.St.-Hil., together with their anti-inflammatory and antitumor activities, suggesting a mechanism of action. The cytostatic activity was observed in several human tumor cell lines, with selectivity towards lung cells. The study of the cell death mechanisms promoted by the active fraction FAIII6-8 towards these cells showed non-apoptotic and caspase-independent cell death, with rapid increase of ROS levels and expression of RIP1, characterizing necroptosis. Since one of the hallmarks of tumor cells is the evasion of apoptosis, the induction of an alternative cell death is an advantage. In addition, the cytostatic activity was confirmed by cell cycle arrest, loss of mitochondrial membrane potential and JNK activation. In the in vivo experimental models, the active fraction inhibited the development of Ehrlich solid tumor and Lewis Lung Carcinoma. The anti-inflammatory activity of fraction FAIII6-8 was observed in several experimental models such as paw edema, ear edema, peritonitis and colitis. In these models there was reduction of the first phase of acute inflammation, reduction of leukocyte migration and decreased expression of several pro-inflammatory mediators, such as IL-6, IL-17, COX-2 among others. The data from colitis model indicated that the treatment disrupted the IL-23 / IL-22 / IL-17 axis. In the colitis-associated carcinogenesis model, the treatment with FAIII6-8 prevented the development of tumors only when administered in the early stages of the carcinogenic process, when inflammation acts as a promoter. In accordance, there was only a mild activity of the fraction FAIII6-8 in the carcinogenic model not preceded by inflammation. In addition to these data, the essential oil from this specie was applied in tumor cell lines and showed marked cytostatic activity. Therefore, the Brazilian specie "Croton campestris" A.St.-Hil. represents a source of promising antitumor and anti-inflammatory agents (AU) | |
| FAPESP's process: | 11/22457-7 - Isolation, identification and mechanism of action of anticancer active principles of Croton campestris A.St.-Hil. |
| Grantee: | Paula Araujo Monteiro |
| Support Opportunities: | Scholarships in Brazil - Doctorate |