title: Bothrops jararacaandBothrops erythromelasSnake Venoms Promote Cell Cycle Arrest and Induce Apoptosis via the Mitochondrial Depolarization of Cervical Cancer Cells.
abstract: Bothrops jararaca(BJ) andBothrops erythromelas(BE) are viper snakes found in South-Southeast and Northeast regions of Brazil, respectively. Snake venoms are bioactive neurotoxic substances synthesized and stored by venom glands, with different physiological and pharmacological effects, recently suggesting a possible preference for targets in cancer cells; however, mechanisms of snakes have been little studied. Here, we investigated the mechanism responsible for snake crude venoms toxicity in cultured cervical cancer cells SiHa and HeLa. We show that BJ and BE snake crude venoms exert cytotoxic effects to these cells. The percentage of apoptotic cells and cell cycle analysis and cell proliferation were assessed by flow cytometry and MTT assay. Detection of mitochondrial membrane potential (Rhodamine-123), nuclei morphological change, and DNA fragmentation were examined by staining with DAPI. The results showed that both the BJ and BE venoms were capable of inhibiting tumor cell proliferation, promoting cytotoxicity and death by apoptosis of target SiHa and HeLa cells when treated with BJ and BE venoms. Furthermore, data revealed that both BJ venoms in SiHa cell promoted nuclear condensation, fragmentation, and formation of apoptotic bodies by DAPI assay, mitochondrial damage by Rhodamine-123, and cell cycle block in the G1-G0 phase. BJ and BE venoms present anticancer potential, suggesting that bothBothropsvenoms could be used as prototypes for the development of new therapies.
authors.affiliation: Programa de Pós Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil.
authors.forename: Emanuelly
authors.identifier: 0000-0003-4673-9209
authors.initials: E
authors.lastname: Bernardes-Oliveira
authors.affiliation: Programa de Pós Graduação em Ciências da Saúde, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil.
authors.forename: Dayanne Lopes
authors.initials: DL
authors.lastname: Gomes
authors.affiliation: Programa de Pós Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Martelli Palomino
authors.affiliation: Programa de Pós Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil.
authors.forename: Kleber
authors.identifier: 0000-0003-3927-444X
authors.initials: K
authors.lastname: Juvenal Silva Farias
authors.affiliation: Laboratório de Imunoquímica, Instituto Butantan, São Paulo, SP, Brazil.
authors.forename: Wilmar Dias
authors.initials: WD
authors.lastname: da Silva
authors.affiliation: Programa de Pós Graduação em Ciências da Saúde, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil.
authors.forename: Hugo Alexandre Oliveira
authors.identifier: 0000-0003-3881-2410
authors.initials: HA
authors.lastname: Rocha
authors.affiliation: Departamento de Tocoginecologia, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil.
authors.forename: Ana Katherine
authors.initials: AK
authors.lastname: Gonçalves
authors.affiliation: Programa de Pós Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil.
authors.forename: Matheus de Freitas
authors.initials: MF
authors.lastname: Fernandes-Pedrosa
authors.affiliation: Programa de Pós Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil; Maternidade Escola Januário Cicco (MEJC), Natal, RN, Brazil.
authors.forename: Janaina Cristiana de Oliveira
authors.initials: JC
authors.lastname: Crispim