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| Author(s): |
Paula Pereira de Paiva
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: | 2016-08-26 |
| Examining board members: |
João Ernesto de Carvalho;
Valéria Helena Alves Cagnon;
Patricia Moriel;
Severino Matias de Alencar;
Alexandre Bechara
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| Advisor: | Mary Ann Foglio; João Ernesto de Carvalho |
| Abstract | |
Cancer is the second leading cause of mortality worldwide, with progressive increase in the number of cases, highlighting the need of new chemotherapeutic with greater effectiveness and, whenever possible, with fewer side effects. Natural products have shown to be a rich source of new chemotherapeutic agents, mainly by action of multi-target activity. In this context, preliminary studies in our research group showed that the leaves¿ crude ethanol extract (EBE) of Boehmeria caudata Sw. was effective in vitro antiproliferative activity test against cultured human cancer cell lines and non-cancer cells lines. Thus, the present study aimed to evaluate the antitumor and anti-inflammatory potencial of alkaloids rich fration obtained of B. caudata with in vitro and in vivo experiments. The results showed that the potential antiproliferative activity of B. caudata could be attributed to phenanthroquinolizidines alkaloids (FA). Among the tested cell lines, one of the most sensitive was the lung tumor line (NCI-H460) with 0,17 µg mL-1 of total growth inhibiton; considering that in Brazil, lung cancer is the second most prevalent among men and the fourth among women, this cell line was chosen to studies the mechanism of action. Thus, FA promoted cell cycle arrest in NCI-H460 human lung cancer cells, with increase in the subpopulation at the G2/M, phase 24 and 48 hrs after treatment, promoting also an slight increase in cell subpopulations with exposure of phosphatidylserine residues without loss of permeability membrane, 24 h after treatment and those with exposure and loss of membrane integrity 36 hrs after treatment. Furthermore, FA decreases the ability NCI-H460 cells recuperation and replication, after the withdrawal of treatment, strengthening the possible FA effect on the cell cycle. In vivo experiments, with both EBE and FA reduced the progression of Ehrlich solid tumor in Balb/c mice, with some clinical signs of toxicity only after treatment with EBE. Furthermore, FA also reduced the inhibition and/or migration of neutrophil mouse paw when evaluated with Ehrlich solid tumor. EB and FA were also assessed in inflammation experimental models. Thus, EBE showed antiedematogenic effect on carrageenan-induced paw edema model only in the lowest and intermediate dose, whereas the anti-inflammatory effect of FA was independent of dose. In the croton oil-induced ear edema model, both EBE and FA were, effective, independent of the administration route (oral, intraperitoneal and topical) suggesting a nonspecific inhibitory action on LOX/COX. The accumulation of myeloperoxidase per milligram of tissue and the FA inhibition of the activation e/or migration of neutrophil to the inflamed site. Finally, these results indicate that the aerial parts of B. caudata are a promising source of phenanthroquinolizidines alkaloids with potential use in anti-inflammatory and anti-tumor therapies; further studies will provide knowledge of cellular and molecular mechanisms involved in the pharmacological activities evidenced in this study (AU) | |
| FAPESP's process: | 11/22458-3 - Isolation, identification and mechanism of action of fractions and active principles of Boehmeria caudata Sw with anticancer activity. |
| Grantee: | Paula Pereira de Paiva |
| Support Opportunities: | Scholarships in Brazil - Doctorate |