Silymarin Prevents UV Irradiation-Induced A375-S2 Cell Apoptosis

Li, Lin Hao; Li, Wu; Zhou, Bei; Wu, Zhiyong; Tashiro, Shin Ichi; Onodera, Satoshi; Uchiumi, Fumiaki; Ikejima, Takashi

doi:10.1248/bpb.27.1031

Cited by 30 publications

(25 citation statements)

References 26 publications

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“…In the present study, silymarin significantly reduced caspase-3 and -9, HIF-1α and iNOS expression levels in rats following lung I/R injury. Similarly, Li et al (30) previously reported that silymarin reduced the UV-irradiated caspase-3 and -9 activities in A375-S2 cells, and Atawia et al (31) demonstrated that silymarin reduced the production of inflammatory mediators by downregulation of HIF-1α, iNOS and NF-κB. Kim et al (32) demonstrated that silymarin inhibits NO and iNOS production in pancreatic β cells.…”

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confidence: 83%

Modulatory effect of silymarin on pulmonary vascular dysfunction through HIF-1α-iNOS following rat lung ischemia-reperfusion injury

Jin

Zhao

Zhang

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Silymarin is a traditional therapeutic used to protect the liver, acting to oppose lipid peroxidation, to enhance liver regeneration and functioning as an antioxidant. However, the effects of silymarin on pulmonary vascular dysfunction have not been investigated. In the present study, the modulatory effects of silymarin on pulmonary vascular dysfunction and the underlying mechanisms behind this were investigated in a lung ischemia-reperfusion (I/R) injury rat model. Male Sprague Dawley rats were randomly divided into 3 groups, including: i) A control group (n=10); ii) an I/R group (n=10); and iii) a silymarin-treated group (n=10). All experimental rats received 250 mg/kg/day of silymarin for 8 days. Silymarin was demonstrated to markedly improve lung I/R-induced pulmonary vascular dysfunction and lung moisture. Following silymarin treatment, inflammation and oxidative stress in the lung I/R-injury rats were demonstrably suppressed. Treatment with silymarin also inhibited the activation of caspase-3 and -9, and hypoxia inducible factor-1α (HIF-1α) and inducible nitric oxide synthase (iNOS) protein expression in the lung I/R-injury rats. Silymarin was concluded to impact upon pulmonary vascular dysfunction through the HIF-1α-iNOS pathway in the lung I/R injury rat model.

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mentioning

confidence: 83%

Modulatory effect of silymarin on pulmonary vascular dysfunction through HIF-1α-iNOS following rat lung ischemia-reperfusion injury

Jin

Zhao

Zhang

et al. 2016

Experimental and Therapeutic Medicine

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“…After 24 h of incubation, the cells were treated with or without 80 µmol/L oridonin for 24 h. The cells were then incubated with 5 mmol/L Hoechst 33258 at 37 °C for 30 min, and the nuclear changes of fluorescence were observed by OLYM-PUS IX70 reverse fluorescence microscopy (Olympus, Tokyo, Japan) at excitation wavelength 350 nm with emission filter 460 nm [26] .…”

Section: Cell Growth Inhibition Assaymentioning

confidence: 99%

“…Staining with Annexin V/PI was used to measure apoptosis. The cells were fixed with 100 µL binding buffer and treated with 2 µL Annexin V-FITC solution (20 mg/L) at 4 °C for 20 min; they [26] . Next, the samples were analyzed using a FACScan flow cytometer (Becton Dickinson, Franklin Lakes, NJ, USA).…”

Section: Cell Growth Inhibition Assaymentioning

confidence: 99%

Reactive oxygen species contribute to oridonin-induced apoptosis and autophagy in human cervical carcinoma HeLa cells

Zhang

Tashiro

et al. 2011

Acta Pharmacol Sin

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Aim: To investigate the role of reactive oxygen species (ROS) in oridonin-induced apoptosis and autophagy in HeLa cells. Methods: The cell viability was measured using MTT assay. Morphological changes of apoptosis and autophagy were examined using Hoechst 33258 staining and monodansylcadaverine (MDC) staining, respectively. The mitochondrial membrane potential (ΔΨm) was measured using fluorescent dye rhodamine 123. DCF-induced fluorescence was used to measure the intracellular ROS level. Protein expression was examined using Western blot. In the presence of the specific autophagy inhibitor 3-MA (2 mmol/L), the oridonin-induced apoptosis was significantly enhanced. Treatment of HeLa cells with oridonin (20-120 μmol/L) induced intracellular ROS generation in a concentration-dependent manner. In the presence of the ROS scavenger NAC (5 mmol/L), the oridinin-induced ROS generation was markedly reduced. NAC (5 mmol/L) or nonthiol antioxidant catalase (1000 U/mL) significantly reduced the oridonin-induced inhibition of cell growth and apoptosis. Furthermore, oridonin significantly reduced ΔΨm, which was blocked by NAC. Oridonin markedly increased Bax expression in mitochondria, and decreased Bcl-2 expression in both the cytosol and mitochondria. Oridonin also markedly increased the phosphorylation of Bcl-2 in the cytosol. All the effects were blocked by NAC. Oridonin increased the levels of caspase-3 and caspase-8, and decreased the expression of pro-caspase 3 and pro-caspase 9, which were blocked by NAC. Conclusion: ROS plays a critical role in oridonin-induced apoptosis and autophagy.

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“…3,4) These possible mechanisms of the inhibitory effect of silibinin on UV-induced HaCaT cell apoptosis remains to be elucidated. Silymarin has been used in the clinical treatment of hepatic diseases 25,26) and pharmacologic studies indicate that silymarin is not toxic even at high doses.…”

Section: Discussionmentioning

confidence: 99%

“…Our previous study demonstrated that silymarin was found to have an anti-apoptotic effect against UV irradiation in human malignant melanoma A375-S2 cells. 3,4) Therefore, in this study, we investigated whether silibinin, the major active compound in silymarin, has a preventive effect against UV-induced skin damage in vitro by employing HaCaT human immortalized keratinocyte cells.…”

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confidence: 99%

Silibinin Prevents UV-Induced HaCaT Cell Apoptosis Partly through Inhibition of Caspase-8 Pathway

Tashiro

et al. 2006

Biological & Pharmaceutical Bulletin

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Silymarin is a polyphenolic flavonoid from milk thistle (Silybum marianum), which has anti-inflammatory, cytoprotective, and anticarcinogenic effects. 1) In this study, we assessed the effect of silibinin (Fig. 1), the major active compound in silymarin, on ultraviolet light (UV)-induced cell apoptosis in HaCaT cells, a human keratinocyte cell line. Pretreatment with silibinin 500 m mM significantly inhibited UV-induced apoptosis in HaCaT cells after 9 h incubation. The expression of Fas-associating protein with death domain (FADD), a downstream molecule of the death receptor pathway, was completely eliminated by silibinin treatment in UV-irradiated HaCaT cells, followed by inhibition of cleavage of procaspase-8, whose activation induced cell apoptosis 2) and decreased the release of cytochrome c from mitochondria. The caspase-8 inhibitor z-IETD-fmk at 10 m mM increased the ratio of UV-irradiated HaCaT cell viability, suggesting that UV-induced HaCaT cell apoptosis was partially due to activation of the caspase-8 pathway. Moreover, UV-induced cleavage of procaspase-3 and digestion of its substrates, the inhibitor of caspase-activated DNase (ICAD) and poly-(ADP-ribose) polymerase (PARP), were also reduced by silibinin pretreatment. While unexpectedly, it was found in our study that pretreatment with silibinin increased HaCaT cell death by CD95 agonistic antibody CH11. Consequently, the protective effect of silibinin against UV irradiation in HaCaT cells is exerted by inactivation of caspase-8 after direct downregulation of FADD expression, resulting in blockage of UV-induced apoptosis.

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Silymarin Prevents UV Irradiation-Induced A375-S2 Cell Apoptosis

Cited by 30 publications

References 26 publications

Modulatory effect of silymarin on pulmonary vascular dysfunction through HIF-1α-iNOS following rat lung ischemia-reperfusion injury

Modulatory effect of silymarin on pulmonary vascular dysfunction through HIF-1α-iNOS following rat lung ischemia-reperfusion injury

Reactive oxygen species contribute to oridonin-induced apoptosis and autophagy in human cervical carcinoma HeLa cells

Silibinin Prevents UV-Induced HaCaT Cell Apoptosis Partly through Inhibition of Caspase-8 Pathway

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