Coumestrol suppresses hypoxia inducible factor 1α by inhibiting ROS mediated sphingosine kinase 1 in hypoxic PC-3 prostate cancer cells

Cho, Sung-Yun; Cho, Sun-Mi; Park, Eunkyung; Kim, Bonglee; Sohn, Eun Jung; Oh, Bumsuk; Lee, Eun-Ok; Lee, Hyo‐Jeong; Kim, Sung‐Hoon

doi:10.1016/j.bmcl.2014.03.084

Cited by 33 publications

(26 citation statements)

References 35 publications

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“…Previous studies have reported various effects of coumestrol, showing for example that coumestrol suppresses hypoxiainducible factor-1α by inhibiting reactive oxygen species (ROS)-mediated sphingosine kinase 1 activity, 11) and induces mitochondrial biogenesis by activating Sirt1. 12) However, studies of the efficacy of coumestrol on skin are limited.…”

Section: Discussionmentioning

confidence: 99%

Coumestrol Down-Regulates Melanin Production in Melan-a Murine Melanocytes through Degradation of Tyrosinase

Hwang

Park

et al. 2017

Biological & Pharmaceutical Bulletin

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Pigmentation reflects skin darkening caused by melanin production, but excessive melanin synthesis may cause problems, such as melasma, solar lentigo, dark spots, and freckles. Considerable effort has been devoted to alleviating these undesired symptoms through the development of safe and effective depigmenting agents. Coumestrol, a plant-derived natural isoflavone with an estrogen-like structure and actions, is known to have anti-aging ability, but its potential depigmenting efficacy has not been evaluated. In the present study, we investigated the effects of coumestrol on melanin synthesis in normal melan-a murine melanocytes. Coumestrol significantly reduced melanin synthesis in a concentration-dependent manner up to a concentration of 25 µM without causing cytotoxicity. It also brightened tissue in an artificial skin model (MelanoDerm) that incorporates both human keratinocytes and melanocytes. Interestingly, although coumestrol did not inhibit tyrosinase activity or transcript level in melan-a cells, it clearly decreased the expression level of tyrosinase protein at a concentration of 25 µM. This coumestrol-induced reduction in tyrosinase protein levels was prevented by pretreatment with the proteasome inhibitor MG-132 or the lysosomal proteolysis inhibitor chloroquine. Collectively, our findings indicate that coumestrol exerts an inhibitory effect on melanin synthesis in melan-a cells, at least in part, through degradation of tyrosinase. These findings suggest that coumestrol is a good candidate for use in depigmentary reagents from a cosmetic and clinical perspective.

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Section: Discussionmentioning

confidence: 99%

Coumestrol Down-Regulates Melanin Production in Melan-a Murine Melanocytes through Degradation of Tyrosinase

Hwang

Park

et al. 2017

Biological & Pharmaceutical Bulletin

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“…The Sphingosine kinase activity assay method was previously described in our other study [37, 38]. Protein extracts (30 μg) were reacted in reaction buffers, 100 μM of sphingosine, and 10 μM of ATP, for 1 h at 37 °C, and then to stop the kinase reaction, a luminescence attached ATP detector was added.…”

Section: Methodsmentioning

confidence: 99%

Anti-cancer effect of pristimerin by inhibition of HIF-1α involves the SPHK-1 pathway in hypoxic prostate cancer cells

et al. 2016

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BackgroundHypoxia is a typical character of locally advanced solid tumours. The transcription factor hypoxia-inducible factor 1α (HIF-1α) is the main regulator under the hypoxic environment. HIF-1α regulates various genes to enhance tumour progression, angiogenesis, and metastasis. Sphingosine kinase 1 (SPHK-1) is a modulator of HIF-1α.MethodsTo investigate the molecular mechanisms of pristimerin in association with SPHK-1 pathways in hypoxic PC-3 cancer cells. Vascular endothelial growth factor (VEGF) production, cell cycles, and SPHK-1 activity were measured, and western blotting, an MTT assay, and an RNA interference assay were performed.ResultsPristimerin inhibited HIF-1α accumulation in a concentration- and-time-dependent manner in hypoxic PC-3 cells. Pristimerin suppressed the expression of HIF-1α by inhibiting SPHK-1. Moreover, inhibiting SPHK-1 with a sphingosine kinase inhibitor enhanced the suppression of HIF-1α, phosphorylation AKT, and glycogen synthase kinase-3β (GSK-3β) by pristimerin under hypoxia. Furthermore, a reactive oxygen species (ROS) scavenger enhanced the inhibition of HIF-1α and SPHK-1 by pristimerin.ConclusionTaken together, these findings suggest that pristimerin can exert an anti-cancer activity by inhibiting HIF-1α through the SPHK-1 pathway.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2730-2) contains supplementary material, which is available to authorized users.

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“…Other studies have shown that coumestrol has anticarcinogenic effects against several cancer cell lines [14,15]. Despite the fact that several flavonoids show antiviral effects against a wide range of viruses, the antiviral activity of soy isoflavonoids has not been sufficiently investigated.…”

Section: Introductionmentioning

confidence: 99%

Antiherpes evaluation of soybean isoflavonoids

et al. 2015

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The antiviral effects of soybean isoflavonoids have been investigated recently, especially those of genistein. It has been reported that this isoflavone is able to inhibit herpes simplex virus (HSV) replication, which is associated with skin and epithelial mucosa infections. The treatment of these infections with antiherpes drugs has resulted in the emergence of resistant viral strains. Based on this evidence, the aim of this study was to investigate the anti-HSV effects of soybean isoflavonoids: daidzein, genistein, glycitein, and coumestrol. Genistein and coumestrol inhibited HSV-1 (KOS and 29R strains, which are acyclovir sensitive and acyclovir resistant, respectively) and HSV-2 (333 strain) replication, whereas no antiviral effects were detected for daidzein and glycitein. The mechanisms of action were evaluated by different methodological strategies. Coumestrol affected the early stages of viral infection, and both compounds were able to reduce HSV-1 protein expression, as well as HSV-2 cell-to-cell spread.

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Coumestrol suppresses hypoxia inducible factor 1α by inhibiting ROS mediated sphingosine kinase 1 in hypoxic PC-3 prostate cancer cells

Cited by 33 publications

References 35 publications

Coumestrol Down-Regulates Melanin Production in Melan-a Murine Melanocytes through Degradation of Tyrosinase

Coumestrol Down-Regulates Melanin Production in Melan-a Murine Melanocytes through Degradation of Tyrosinase

Anti-cancer effect of pristimerin by inhibition of HIF-1α involves the SPHK-1 pathway in hypoxic prostate cancer cells

Antiherpes evaluation of soybean isoflavonoids

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