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Previous issue date: 2016-07-27 / C?ncer cervical (CC) ? o terceiro tipo de c?ncer mais comum em mulheres no mundo todo e a quarta principal causa de morte em mulheres nos pa?ses em desenvolvimento. Os Papilomav?rus humano (HPV) de alto risco tais como HPV 16, 18, 31 e 33 s?o o principal fator de risco para esse tipo de c?ncer. Entre estes, o HPV-16 e -18 s?o respons?veis por quase 70% dos casos de CC. Quimioterapia com compostos ? base de platina em combina??o com a radioterapia ou a cirurgia ? o tratamento de escolha para CC, mas sua efic?cia ? limitada, especialmente em est?gios avan?ados da doen?a. Al?m disso, estes tratamentos podem facilmente levar a rea??es adversas e resist?ncia ?s drogas. Assim, a busca por novos agentes antitumorais seletivos e de alta efic?cia para o tratamento deste tipo de tumor ? necess?ria. Croton blanchetianus (CB), popularmente conhecida como ?marmeleiro preto?, ? um arbusto pertencente ? fam?lia Euphorbiaceae e amplamente disseminado no nordeste brasileiro. Alguns estudos t?m demonstrado a atividade citot?xica de plantas do g?nero Croton em linhagens tumorais humanas. Contudo, at? o momento, n?o h? nada descrito na literatura quanto ao efeito citot?xico da esp?cie Croton blanchetianus. Assim, o presente trabalho teve como objetivo investigar, in vitro, os efeitos de fra??es obtidas das folhas e raiz de CB nas linhagens de c?ncer cervical humano HeLa e SiHa. As fra??es foram obtidas pelo m?todo de varia??o do pH, a partir do qual foram obtidas duas fra??es ?cidas, uma das folhas (CBaF) e outra da raiz (CBaR), e duas b?sicas, tamb?m das folhas (CBbF) e raiz (CBbR). O perfil fitoqu?mico das fra??es foi avaliado por Cromatografia em camada delgada (CCD). A atividade citot?xica e a avalia??o do tipo de morte celular foram determinados pelos ensaios de MTT e Anexina V/PI, respectivamente, enquanto que para avalia??o de altera??es morfol?gicas nucleares e ensaio do ciclo celular foram utilizados, respectivamente, microscopia de fluoresc?ncia com o corante DAPI e citometria de fluxo. De acordo com os resultados, a maioria das fra??es apresentou terpenos, alcaloides e flavonoides. Al?m disso, todas as fra??es testadas foram capazes de diminuir significativamente a viabilidade celular de HeLa e SiHa de maneira concentra??o e tempo dependentes, promoveram modifica??es morfol?gicas celulares e nucleares, al?m de induzirem apoptose e parada do ciclo celular. Este ? o primeiro estudo que demonstrou os efeitos citot?xicos e pr?-apopt?ticos de CB em linhagens de c?ncer cervical humano. Portanto, CB parece ser uma fonte natural promissora para o desenvolvimento de agentes para o tratamento do CC. No entanto, mais estudos s?o necess?rios para isolar, purificar e elucidar os poss?veis mecanismos de a??o dos compostos ativos. / Cervical cancer (CC) is the third most common cancers in women worldwide and the fourth major cause of cancer death in the woman in developing countries. High-risk human papilloma viruses (HPVs) such as HPV 16, 18, 31 and 33 have been attributed to be the major risk factors for cervical cancer, out of which HPV-16 and -18 account for almost 70% of the cancers. Platinum-based chemotherapy in combination with radiotherapy or surgery is now mainly used to treat CC, but the efficacy is limited especially in advanced-stage disease. Furthermore, these treatments could easily lead to adverse reactions and drug resistance. Thus, it is necessary to seek antitumor drugs of high efficacy for the treatment of this kind of tumor. Croton blanchetianus (CB), known as ?black marmeleiro?, belongs to the family Euphorbiaceae and it is a widely disseminated shrub found in northeast Brazil. Some studies have demonstrated cytotoxic activity of plants of this genus against human tumor cell lines. However, to date, there is nothing described in the literature as to the cytotoxic effect of the Croton blanchetianus. Therefore, the present study aimed to investigate, in vitro, the effects of leaves and root fractions from Croton blanchetianus (CB) against human cervical cancer HeLa and SiHa cells. Fractions were obtained by pH variation method, from which were obtained two acidic fractions, one of the leaves (CBaF) and root (CBaR) and two basic also obtained from leaves (CBbF) and root (CBbR). Phytochemical screening was evaluated by thin layer chromatography. Cytotoxic activity and cell death evaluation were determined with MTT and annexin V/PI assays by flow cytometry, respectively. Nuclear morphological changes were evaluated by fluorescence with DAPI stanning and flow cytometry was used to cycle assay. According to results, most of the fractions exhibited terpenoids, alkaloids and flavonoids. All fractions decreased significantly cell viability of HeLa and SiHa cells in a concentration- and time-dependent manner, promoted cellular and nuclear morphological changes and induced apoptosis and cell cycle arrest. This is the first study that demonstrated cytotoxic and pro apoptotic effects of CB on HeLa and SiHa cells. Therefore, CB appears to be a valuable natural source for the development of agents for the treatment of CC. However, more studies are needed to isolate, purify and elucidate the possible action mechanisms of the active compounds.
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufrn.br:123456789/22598 |
| Date | 27 July 2016 |
| Creators | Carvalho, Kleyton Thiago Costa de |
| Contributors | 91430364491, http://lattes.cnpq.br/2644540835478572, Luchessi, Andr? Ducati, 30489740839, http://lattes.cnpq.br/4420863418928278, Donadi, Eduardo Ant?nio, 74759337849, http://lattes.cnpq.br/8778713382135771, Freitas, Janaina Cristiana de Oliveira Crispim |
| Publisher | PROGRAMA DE P?S-GRADUA??O EM CI?NCIAS FARMAC?UTICAS, UFRN, Brasil |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Source | reponame:Repositório Institucional da UFRN, instname:Universidade Federal do Rio Grande do Norte, instacron:UFRN |
| Rights | info:eu-repo/semantics/openAccess |
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