Production of hydrogen peroxide and redox cycling can explain how sanguinarine and chelerythrine induce rapid apoptosis

Matkar, Smita; Wrischnik, Lisa A.; Hellmann-Blumberg, Utha

doi:10.1016/j.abb.2008.05.019

Cited by 63 publications

(43 citation statements)

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“…The released Cyt-c together with apaf-1 activates caspase 9 and subsequently caspase 3 to trigger the apoptotic cascade (Li et al, 1997). Many studies have shown that CHE can induce the release of Cyt-c from the mitochondria in different cell lines (Yamamoto et al, 2001;Matkar et al, 2008). In the present study, we also observed that CHE markedly increased the release of Cyt-c from the mitochondria to the cytosol in SMMC-7721 cells.…”

Section: Discussionsupporting

confidence: 79%

“…CHE was found to exhibit antiproliferative and apoptotic activities against various human cancer cell lines, including squamous cell carcinoma (HNSCC) (Chmura et al, 2000), human leukemia (Chmura et al, 1996;Freemerman et al, 1996), human breast cancer (MCF-7), human colon carcinoma (HCT116) (Chan et al, 2003), human uveal melanoma (OCM-1) (Kemény-Beke et al, 2006), human neuroblastoma (SH-SY5Y) cell lines and neonatal rat cardiac myocytes (Yamamoto et al, 2001). It has been shown that CHE rapidly induces apoptosis through Cyt-c release from mitochondria and generation of reactive oxygen species (Yamamoto et al, 2001;Matkar et al, 2008), which are important regulators of apoptosis. Furthermore, it induces cell cycle arrest and mitochondrial-mediated apoptosis (Maliková et al, 2006a(Maliková et al, , 2006bVrba et al, 2008).…”

Section: Introductionmentioning

confidence: 97%

“…Due to its apoptotic potential, CHE was considered an attractive candidate for cancer therapy (Chan et al, 2003;Kemény-Beke et al, 2006;Maliková et al, 2006;Matkar et al, 2008). However, there is much to learn regarding the mechanism of apoptosis induced by CHE, and also little is known regarding the effect of CHE on SMMC-7721 cells.…”

Section: Introductionmentioning

confidence: 97%

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Induction of apoptosis by chelerythrine chloride through mitochondrial pathway and Bcl-2 family proteins in human hepatoma SMMC-7721 Cell

et al. 2011

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The objective of this study was to evaluate the antitumor activity of chelerythrine chloride (CHE) and investigate its potential apoptotic induction mechanism in SMMC-7721 cells. Our results suggested that the proliferation of SMMC-7721 cells was inhibited by CHE in a time and dose dependent manner, with a significant accumulation in S phase, and the cells exhibited typical apoptotic features. Moreover, CHE remarkably induced apoptosis by disruption of the mitochondrial membrane potential, release of Cyt-c, activation of caspase-3, and cleavage of poly-ADP-ribose polymerase in a dose dependent manner. Furthermore, the expression of Bcl-xl was downregulated while Bax and Bid expression was upregulated, and no variation was found for Bcl-2. These results indicated that CHE may play an important role in suppression of tumor growth by inducing apoptosis in human hepatoma cells via the activation of a mitochondrial pathway and regulating the expression of Bcl-2 family proteins.

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Section: Discussionsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 97%

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Induction of apoptosis by chelerythrine chloride through mitochondrial pathway and Bcl-2 family proteins in human hepatoma SMMC-7721 Cell

et al. 2011

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“…Further, it was reported that this alkaloid generated increased production of reactive oxygen species (ROS) and depletion of cellular antioxidants, such as reduced glutathione (GSH) (Matkar et al, 2008). The mechanism suggested for sanguinarine-induced apoptosis is based on the activation of caspases regulated by different proteins, including members of the Bcl-2 family (Lee et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

The cytotoxic activity of sanguinarine in C32 human amelanotic melanoma cells

Cojocaru¹,

Stan²,

Anton³

et al. 2016

Turk J Biol

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Sanguinarine, an alkaloid present in various medicinal plants, has been associated with detrimental effects on different types of cancer cells. The aim of our study was to analyze the cytotoxic effects of sanguinarine on C32 human amelanotic melanoma cells. The cells were exposed to various concentrations of sanguinarine (0.5, 1, and 2 µM) for 24 h and displayed a dose-dependent decrease in cell viability; the sanguinarine-induced oxidative stress in C32 cells affected the activity of antioxidant enzymes and generated lipid peroxidation. Moreover, we observed an enhanced expression of heat shock proteins 60, 70, and 90 in response to the stress exerted by this alkaloid. The increased p53 protein expression and Bax/Bcl-2 ratio revealed the susceptibility of C32 cells to apoptosis. Our study demonstrated that sanguinarine induced cytotoxicity in melanoma cells that ultimately resulted in cell death. These results emphasize the antigrowth efficiency of sanguinarine against amelanotic melanoma cells, but further research is needed in order to obtain more potent antitumor effects of this alkaloid.

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“…Dessa forma, a purificação e o armazenamento desses compostos não foi possível e estratégias para melhorar estes processos devem ser feitas para a obtenção desses análogos. HELLMANN-BLUMBERG, 2008;SLANINOVÁ et al, 2007;ZHANG et al, 2012 A determinação da curva dose-resposta e cálculo de IC50 para o 2f em A549 foi realizado com cinco pontos e concentração máxima de 150 µM. Essa concentração ultrapassa os valores escolhidos para a triagem dos compostos nas outras linhagens celulares.…”

Section: Síntese E Caracterização De Aminas Terciáriasunclassified

Potenciais candidatos a novos antineoplásicos: síntese e avaliação da atividade antitumoral de análogos da queleritrina planejados por simplificação molecular

Yang¹

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Production of hydrogen peroxide and redox cycling can explain how sanguinarine and chelerythrine induce rapid apoptosis

Cited by 63 publications

References 58 publications

Induction of apoptosis by chelerythrine chloride through mitochondrial pathway and Bcl-2 family proteins in human hepatoma SMMC-7721 Cell

Induction of apoptosis by chelerythrine chloride through mitochondrial pathway and Bcl-2 family proteins in human hepatoma SMMC-7721 Cell

The cytotoxic activity of sanguinarine in C32 human amelanotic melanoma cells

Potenciais candidatos a novos antineoplásicos: síntese e avaliação da atividade antitumoral de análogos da queleritrina planejados por simplificação molecular

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