Investigation of Ehrlich ascites tumor cell death mechanisms induced by Synadenium umbellatum Pax.

Mota, Mariana Flávia da; Benfica, Polyana Lopes; Batista, Aline Carvalho; Martins, Frederico Severino; Paula, José Realino de; Valadares, Marize Campos

doi:10.1016/j.jep.2011.04.055

Cited by 37 publications

(18 citation statements)

References 52 publications

(51 reference statements)

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“…The toxicity of the Synadenium genus has been demonstrated, mainly based on the evaluation of extracts from the aerial parts of the plant (Castro and Valadares, 2005;Valadares et al, 2007;Cunha et al, 2009;Mota et al, 2012) but few studies have reported the potential effect of the latex, which is popularly used for therapeutic purposes, as reported in this present study. Melo-Reis et al (2011) showed that Synadenium umbelattum latex presents cytotoxic and mutagenic potential (concentration-dependent), and in the same species, Oliveira et al (2005) found a relatively low LD50 value (110-168 mg/Kg), which shows that substantial care should be taken in its empirical use due to its high toxicity.…”

Section: Discussionmentioning

confidence: 63%

Antitumoural effect of Synadenium grantii Hook f. (Euphorbiaceae) latex

Oliveira¹,

Munhoz²,

Lemes³

et al. 2013

Journal of Ethnopharmacology

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Section: Discussionmentioning

confidence: 63%

Antitumoural effect of Synadenium grantii Hook f. (Euphorbiaceae) latex

Oliveira¹,

Munhoz²,

Lemes³

et al. 2013

Journal of Ethnopharmacology

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“…The images were taken using the AxioCam MRc Carl Zeiss camera and AxioVs40 V 4.7.2.0 Carl Zeiss software (Carl Zeiss, Jena, TH, Germany). In addition, nuclear changes were assessed using the DNA binding dye Hoechst 33342 and the apoptotic index was obtained as described by our laboratory (Mota et al 2012) using a fluorescence microscope (DMI 4000 B Leica Microsystems, Bannockburn, IL) coupled to the software LAS-AF filter A4 (blue colour) (Carl Zeiss, Jena, TH, Germany).…”

Section: Cell Morphology Examinationmentioning

confidence: 99%

Eugenia dysentericaDC. (Myrtaceae) exerts chemopreventive effects against hexavalent chromium-induced damagein vitroandin vivo

Ávila

Alvarenga

Ávila

et al. 2016

Pharmaceutical Biology

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Context: Eugenia dysenterica DC. (Myrtaceae) has been widely used in the folk medicine and it presents phytochemicals constituents associated to antioxidant properties. Objective: The objective of this study was to investigate the protective effects of E. dysenterica leaf hydroalcoholic extract (EDE) in vitro and in vivo using AMJ2-C11 cells and Swiss mice exposed to hexavalent chromium [Cr(VI)], respectively. Materials and methods: AMJ2-C11 cells were pretreated with EDE and exposed to Cr(VI) to evaluate cytotoxicity and the pathways involved in the chemopreventive effects of the extract. Mice were daily pretreated with EDE and then exposed to Cr(VI). Survival analysis, histopathological examination and determination of Cr levels in biological tissues were carried out. Results: In vitro studies showed that pretreatment of the AMJ2-C11 cells with EDE protected against the cytotoxicity and oxidative stress induced by Cr(VI). Consequently, the pretreatment with EDE reduced reactive oxygen species and apoptosis triggered by Cr(VI), probably by a marked antioxidant and chelating activities demonstrated by EDE. Regarding in vivo studies, pretreatment for 10 days with EDE increased survival of the mice exposed to Cr(VI). In addition, EDE prevented liver and kidney pathological damages, in parallel with reduction in chromium levels found in these organs and plasma. EDE also showed a marked antioxidant potential associated with the presence of polyphenols, especially flavonoids and tannins, as confirmed by HPLC-PDA. Conclusion: The study showed that EDE protects against Cr(VI)-induced damage in vitro and in vivo supporting further studies for the development of therapeutic products applied to prevent the damage induced by toxic metals, especially Cr(VI).

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“…Plant families possessing bioactive compounds, particularly terpenes, have shown antitumor properties (Mota et al, 2012). The cytotoxic activity of the Euphorbiaceae has been associated with induction of apoptosis in tumor cells.…”

Section: Discussionmentioning

confidence: 99%

“…The cytotoxic effects found in EAT cells were mediated by activation of the intrinsic and extrinsic pathways of apoptosis. Furthermore, we determined by HPLC that the main constituents of S. umbellatum crude ethanolic extract are flavonoids and terpenes (Mota et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Synadenium umbellatum Pax. promotes cell cycle arrest and induces apoptosis in K-562 leukemia cells

Mota

Benfica

Valadares

2012

Braz. J. Pharm. Sci.

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Chronic myeloid leukemia (CML) is a clonal myeloproliferative disease that shows apoptosis resistance. The introduction of imatinib mesylate has revolutionized the treatment of CML, but imatinib resistance may develop at any time and inevitably leads to disease progression. Synadenium umbellatum Pax. belongs to the Euphorbiaceae family and is popularly used in Brazil for the treatment of cancer. The cytotoxicity of Euphorbiaceae is associated with the ability of these plants and their bioactive compounds to induce apoptotic tumor cell death. Therefore, we aimed to investigate the cytotoxicity and the mechanisms of death induced by S. umbellatum extract in leukemic cells. S. umbellatum cytotoxicity was evaluated by trypan blue exclusion assay and flow cytometric analysis of the cell cycle; the mechanisms involved in K-562 cell death were investigated by light microscopy and flow cytometry. The results demonstrate that S. umbellatum is cytotoxic to leukemic cells in a concentration-dependent manner. Morphological analysis revealed that S. umbellatum treatment induced K-562 cell death by an apoptotic pathway. Furthermore, data indicate ROS overproduction, alterations in mitochondrial membrane potential, phosphatidylserine externalization and activation of caspase 9. Taken together, the results demonstrate that S. umbellatum extract arrested the cell cycle and triggered apoptosis at several levels in K-562 cells. A leucemia mielóide crônica (LMC) é uma doença mieloproliferativa clonal, que apresenta resistência à apoptose. A introdução do mesilato de imatinibe revolucionou o tratamento da LMC, porém a resistência ao imatinibe pode ser desenvolvida em qualquer tempo e, inevitavelmente, leva à progressão da doença. Synadenium umbellatum Pax. pertence à família Euphorbiaceae e é usado popularmente no Brasil para o tratamento do câncer. A citotoxicidade das Euphorbiaceae está associada com a capacidade dessas plantas e seus compostos bioativos em induzir apoptose em células tumorais. Portanto, este trabalho teve como objetivo investigar a citotoxicidade e os mecanismos de morte induzidos por S. umbellatum em células leucêmicas. A citotoxicidade de S. umbellatum foi avaliada pelo ensaio de exclusão do azul de tripano e a análise do ciclo celular foi feita por citometria de fluxo. Os mecanismos envolvidos na morte celular das células K-562 foram investigados por microscopia óptica e por citometria de fluxo. Os resultados demonstraram que S. umbellatum é citotóxico para células leucêmicas de uma maneira dependente da concentração. A análise morfológica revelou que o tratamento com S. umbellatum induziu as célula K-562 à morte por via apoptótica. Além disso, os dados indicam aumento de ERO S , alterações no potencial de membrana mitocondrial, externalização da fosfatidilserina e ativação de caspase 9. Em conjunto, os resultados demonstram que S. umbellatum promoveu retenção do ciclo celular das células K-562 e induziu estas células à morte por apoptose.

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Investigation of Ehrlich ascites tumor cell death mechanisms induced by Synadenium umbellatum Pax.

Cited by 37 publications

References 52 publications

Antitumoural effect of Synadenium grantii Hook f. (Euphorbiaceae) latex

Antitumoural effect of Synadenium grantii Hook f. (Euphorbiaceae) latex

Eugenia dysentericaDC. (Myrtaceae) exerts chemopreventive effects against hexavalent chromium-induced damagein vitroandin vivo

Synadenium umbellatum Pax. promotes cell cycle arrest and induces apoptosis in K-562 leukemia cells

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