P22-05THE DISCOVERY OF A ANTITUMOR ACTIVITY OF THE ALKALOID ERYTHRALIN: INDUCTION OF APOPTOSIS IN SIHA CELLS BY ARRESTING THE CELL CYCLE AT THE G2-M PHASE

22. Cervical neoplasia
C. Miranda 1, H. Rocha 2, T. Guaratini 3, A. Cruz 2, E. Silva 1, R. Giordani 4, J. Crispim 5.
1Doutoranda do Programa de Pós Graduação em Desenvolvimento e Inovação Tecnológica de Medicamentos - UFRN - Natal (Brazil), 2Departamento de Bioquímica - Laboratório de Biotecnologia de Polímeros Naturais - UFRN - Natal (Brazil), 3Lychnoflora Pesquisa e Desenvolvimento em Produtos Naturais Ltda (Brazil), 4Departamento de Farmácia - Laboratório de Farmacognosia - UFRN - Natal (Brazil), 5Maternidade Escola Januário Cicco - Gerência de Ensino e Pesquisa - UFRN - Natal (Brazil)

Background / Objectives

Cervical cancer is the fourth leading cause of cancer death in women worldwide and persistent infection with a high risk human papillomavirus (HR-HPV) is the main etiological factor. Several studies have sought to identify compounds with selective activity for tumor cells that have an apoptotic mechanism of action, therefore it is important investigate bioactive new chemical entities mainly from biodiversity. Erythrina velutina (EV) is a plant native from Brazil popularly known as mulungu. Seeds and barks are used in folk medicine as sedative, anticonvulsant and in sleep disorders. Among the metabolites found in the genus it is highlighted the occurrence of erythrinic alkaloids in several species. In this study, the alkaloid Erythralin was evaluated for anti-tumor activities against human cervical carcinoma cell line (SiHa). 


Methods

Cell viability was quantified by the MTT assay and absorbance (570 nm) by an ELISA reader, in each experiment. The apoptotic cells were evaluated using Propidium and Annexin Iodide staining and analyzed by flow cytometry. Nuclear morphological changes were evaluated by fluorescence with DAPI stanning and flow cytometry was used to cycle assay.


Results

 

The alkaloid Erythralin significantly inhibited (p <0.05) the growth of SiHa cells after 24 and 48 hours. The cell viability assay showed that the inhibitory effects of Erythralin were also consistent with the morphological changes observed under light microscopy in a dose-dependent manner. There was also an increase in apoptotic cells in a dose-dependent manner through cytometric analysis. This is the first study that demonstrated cytotoxic and pro apoptotic effects of Erythralin on SiHa cells. The results also suggest a tendency to stop the cell cycle in the G2-M phase. 


Conclusion

Preliminary studies on mechanism reveal that Erythraline induces apoptosis in SiHa cells by arresting the cell cycle at the G2-M phase. However, further evaluations are necessary for the evaluation of its antitumor properties and mechanisms of action. Our results suggest that compound E. velutina might be a potential candidate for developing novel anti-cancer drugs in the coming future.


References