Anti-Invasive and Anti-Angiogenic Effects of Xanthohumol and Its Synthetic Derivatives

Kim, Jung Ae; Kang, You Ra; Thapa, Dinesh; Lee, Jong Suk; Park, Min A; Lee, Kyung Hee; Lyoo, Won Seok; Lee, Yong Rok

doi:10.4062/biomolther.2009.17.4.422

Cited by 10 publications

(5 citation statements)

References 34 publications

(37 reference statements)

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“…The pyranochalcone xanthohumol C ( 1 ) seems to have a lesser impact on cell survival/proliferation of MEF cells than xanthohumol ( 2 ), as indicated by higher normalized Renilla activity (NRA) (Figure b). The influence of the ring closure of the prenyl group to the pyrano ring on proliferation and cell survival is discussed controversially. ,− However, proteome analyses of xanthohumol C ( 1 ) and xanthohumol ( 2 ) treated MCF-7 cells suggested a divergent mode of action of both compounds …”

Section: Resultsmentioning

confidence: 99%

“…28 Furthermore, xanthohumol C (1) was shown to overrule central nervous system growth inhibitors and facilitates the regeneration of DRG neurons. 59 In addition to neurological targets, xanthohumol C (1) shows an anticarcinogenic effect on hepatome cells, 17 human fibrosarcoma cells, 39,40 and human breast cancer cells. 41 Accordingly, xanthohumol C (1) is a highly interesting natural product which offers itself as a lead structure for further pharmaceutical research concerning neurodegenerative diseases, and therefore, the elucidation of its structure−activity relationship constitutes a crucial element.…”

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confidence: 99%

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Neuroregenerative Potential of Prenyl- and Pyranochalcones: A Structure–Activity Study

et al. 2021

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Loss of neuronal tissue is a hallmark of age-related neurodegenerative diseases. Since adult neurogenesis has been confirmed in the human brain, great interest has arisen in substances stimulating the endogenous neuronal regeneration mechanism based on adult neural stem cells. Medicinal plants are a valuable source of neuroactive small molecules. In the structure–activity study presented here, the activities of prenyl- and pyranochalcones were compared to each other, using a differentiation assay based on the doublecortin promoter sequences. The latter revealed that the pyrano ring is a crucial structural element for the induction of neuronal differentiation of adult neural stem cells, while compounds with a prenyl group show significantly lower activities. Furthermore, a decrease of pro-differentiation activity was observed following structural modifications, such as substitutions on the pyrano ring and on the B-ring of the chalcone. We also initiated the elucidation of the structural characteristics of the newly discovered lead substance xanthohumol C, which correlated with the activation of the doublecortin promoter during neuronal differentiation.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Neuroregenerative Potential of Prenyl- and Pyranochalcones: A Structure–Activity Study

et al. 2021

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“…Xanthohumol C ( 2 ) has been also reported to suppress cancer invasion in relation to matrix metalloproteinase (MMP-2 and MMP-9) expression in HT-1080 human fibrosarcoma cells and inhibited angiogenesis by suppression of vascular endothelial growth factor (VEGF) [ 43 ]. This compound was proven to be the strongest agent promoting neurogenesis, neuroregeneration and neuroprotection among the seven tested hop flavonoids ( 1 , 2 , 3 , 5 , isoxanthohumol C, 6- and 8-prenylnaringenin) [ 44 ].…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Antiproliferative Activity of Minor Hops Prenylflavonoids and New Insights on Prenyl Group Cyclization

et al. 2018

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Synthesis of minor prenylflavonoids found in hops and their non-natural derivatives were performed. The antiproliferative activity of the obtained compounds against some human cancer cell lines was investigated. Using xanthohumol isolated from spent hops as a lead compound, a series of minor hop prenylflavonoids and synthetic derivatives were obtained by isomerization, cyclisation, oxidative-cyclisation, oxidation, reduction and demethylation reactions. Three human cancer cell lines—breast (MCF-7), prostate (PC-3) and colon (HT-29)—were used in antiproliferative assays, with cisplatin as a control compound. Five minor hop prenyl flavonoids and nine non-natural derivatives of xanthohumol have been synthetized. Syntheses of xanthohumol K, its dihydro- and tetrahydro-derivatives and 1″,2″,α,β-tetrahydroxanthohumol C were described for the first time. All of the minor hops prenyl flavonoids exhibited strong to moderate antiproliferative activity in vitro. The minor hops flavonoids xanthohumol C and 1″,2″-dihydroxanthohumol K and non-natural 2,3-dehydroisoxanthohumol exhibited the activity comparable to cisplatin. Results described in the article suggest that flavonoids containing chromane- and chromene-like moieties, especially chalcones, are potent antiproliferative agents. The developed new efficient, regioselective cyclisation reaction of the xanthohumol prenyl group to 1″,2″-dihydroxantohumol K may be used in the synthesis of other compounds with the chromane moiety.

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“…Gelatin zymography was performed for the analysis of the activities of gelatinases secreted into the culture medium as described previously [13,19] with slight modification [18,25]. In brief, culture supernatants containing released MMP-9 were harvested and centrifuged at 17,0009g for 30 s at 4°C.…”

Section: Gelatin Zymographymentioning

confidence: 99%

Urokinase-Type Plasminogen Activator Induces BV-2 Microglial Cell Migration Through Activation of Matrix Metalloproteinase-9

et al. 2010

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In response to brain injury, microglia migrate and accumulate in the affected sites, which is an important step in the regulation of inflammation and neuronal degeneration/regeneration. In this study, we investigated the effect of urokinase-type plasminogen activator (uPA) on the BV-2 microglial cell migration. At resting state, BV-2 microglial cells secreted uPA and the release of uPA was increased by ATP, a chemoattractant released from injured neuron. The migration of BV-2 cell was significantly induced by uPA and inhibited by uPA inhibitors. In this condition, uPA increased the activity of matrix metalloproteinase (MMP-9) and the inhibition of MMP activity with pharmacological inhibitors against either uPA (amiloride) or MMP (phenanthrolene and SB-3CT) effectively prevented BV2 cell migration. Interestingly, the level of MMP-9 protein and mRNA in the cell were not changed by uPA. These results suggest that the increase of MMP-9 activity by uPA is regulated at the post-translational level, possibly via increased activation of the enzyme. Unlike the uPA inhibitor, plasmin inhibitor PAI-1 only partially inhibited uPA-induced cell migration and MMP-9 activation. The incubation of recombinant MMP-9 with uPA resulted in the activation of MMP-9. These results suggest that uPA plays a critical role in BV-2 microglial cell migration by activating pro-MMP-9, in part by its direct action on MMP-9 and also in part by the activation of plasminogen/plasmin cascade.

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Anti-Invasive and Anti-Angiogenic Effects of Xanthohumol and Its Synthetic Derivatives

Cited by 10 publications

References 34 publications

Neuroregenerative Potential of Prenyl- and Pyranochalcones: A Structure–Activity Study

Neuroregenerative Potential of Prenyl- and Pyranochalcones: A Structure–Activity Study

Synthesis and Antiproliferative Activity of Minor Hops Prenylflavonoids and New Insights on Prenyl Group Cyclization

Urokinase-Type Plasminogen Activator Induces BV-2 Microglial Cell Migration Through Activation of Matrix Metalloproteinase-9

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