Diarylheptanoids from lesser galangal suppress human colon cancer cell growth through modulating Wnt/β-catenin pathway

Dong, Guang-Zhi; Lee, So Yoon; Zhao, Hang; Lee, Yu-ih; Jeong, Ji Hye; Jeon, Raok; Lee, Hwa Jin; Ryu, Jae‐Ha

doi:10.1016/j.jff.2015.06.059

Cited by 20 publications

(8 citation statements)

References 29 publications

(38 reference statements)

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“…1B). To test whether GSK-3β is involved in the inhibition of β-catenin transcription, we treated HEK293 cells with LiCl as an inhibitor of GSK-3β14. DFS suppressed LiCl-induced TOPFlash activity in a dose-dependent manner (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…It has been used in traditional oriental medicine to treat fever, hemorrhage, diarrhea, and alcoholism. Recent studies have shown that Alnus japonica has various phytochemicals, such as diarylheptanoids, triterpenoids, and flavonoids91011121314. In this study, we isolated a lignan [(−)-(2R,3R)-1,4-O-diferuloylsecoisolariciresinol, DFS] from Alnus japonica and explored its activity against colon cancer.…”

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confidence: 99%

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A lignan induces lysosomal dependent degradation of FoxM1 protein to suppress β-catenin nuclear translocation

Dong

Jeong

Lee

et al. 2017

Sci Rep

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Colon cancer is one of the most common cancers. In this study, we isolated a lignan [(−)-(2R,3R)-1,4-O-diferuloylsecoisolariciresinol, DFS] from Alnus japonica (Betulaceae) and investigated its biological activity and mechanism of action on colon cancer. DFS reduced the viability of colon cancer cells and induced cell cycle arrest. DFS also suppressed β-catenin nuclear translocation and β-catenin target gene expression through a reduction in FoxM1 protein. To assess the mechanism of the action of DFS, we investigated the effect of DFS on endogenous and exogenous FoxM1 protein degradation in colon cancer cells. DFS-induced FoxM1 protein degradation was suppressed by lysosomal inhibitors, chloroquine and bafilomycin A1, but not by knock-down of proteasomal proteins. The mechanism of DFS for FoxM1 degradation is lysosomal dependent, which was not reported before. Furthermore, we found that FoxM1 degradation was partially lysosomal-dependent under normal conditions. These observations indicate that DFS from A. japonica suppresses colon cancer cell proliferation by reducing β-catenin nuclear translocation. DFS induces lysosomal-dependent FoxM1 protein degradation. This is the first report on the lysosomal degradation of FoxM1 by a small molecule. DFS may be useful in treating cancers that feature the elevated expression of FoxM1.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

A lignan induces lysosomal dependent degradation of FoxM1 protein to suppress β-catenin nuclear translocation

Dong

Jeong

Lee

et al. 2017

Sci Rep

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“…Instead, with the Wnt signals, the level of β-catenin increases, β-catenin in the cytosol accumulates and then translocates to the nucleus and, binds to the T-cell factor (TCF)/lymphoid enhancer factor (LEF) [11]. These transcription factors regulate the expression of specific downstream target genes such as c-myc and Survivin, which are involved in oncogenesis [11–13]. Therefore, the components of the Wnt signalling pathway could be good therapy targets for gastric cancer.…”

Section: Introductionmentioning

confidence: 99%

Umbelliprenin isolated from Ferula sinkiangensis inhibits tumor growth and migration through the disturbance of Wnt signaling pathway in gastric cancer

Zhang

Sun

et al. 2019

PLoS ONE

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The traditional herb medicine Ferula sinkiangensis K. M. Shen ( F . sinkiangensis) has been used to treat stomach disorders in Xinjiang District for centuries. Umbelliprenin is the effective component isolated from F . sinkiangensis which is particularly found in plants of the family Ferula. We previously reported the promising effects of Umbelliprenin against gastric cancer cells, but its anti-migration effect remained unknown. Here we investigated the anti-migration effect and mechanism of Umbelliprenin in human gastric cancer cells. In SRB assay, Umbelliprenin showed cytotoxic activities in the gastric cancer cell lines AGS and BGC-823 in a dose-and-time-dependent manner, while it showed lower cytotoxic activity in the normal gastric epithelium cell line GES-1. During transwell, scratch and colony assays, the migration of tumor cells was inhibited by Umbelliprenin treatment. In gelatin zymography assay, Umbelliprenin could inhibit the expression of MMP2 and MMP9 in tumor cells The expression levels of the Wnt-associated signaling pathway proteins were analyzed with western blots, and the results showed that Umbelliprenin decreased the expression levels of proteins of the Wnt signalling pathway, such as Wnt-2, β-catenin, GSK-3β, p-GSK-3β, Survivin and c-myc. The translocation of β-catenin to the nucleus was also inhibited by Umbelliprenin treatment. In TCF reporter assay, the transcriptional activity of T-cell factor/lymphoid enhancer factor (TCF/LEF) was decreased after Umbelliprenin treatment. The in vivo results suggested that Umbelliprenin induced little to no harm in the lung, heart and kidney. Overall, these data provided evidence that Umbelliprenin may inhibit the growth, invasion and migration of gastric cancer cells by disturbing the Wnt signaling pathway.

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“…Among nutraceuticals, curcumin is an important diarylheptanoid compound, studied extensively for its role in protection against many diseases (Kunnumakkara et al, 2017). Extracts of Alpinia officinarum contain diarylheptanoids, and are prepared as a health supplement capsule (Dong et al, 2015). Diarylheptanoids isolated from Alnus glutinosa have shown to protect noncancerous dividing cells during cancer treatment (Dinić et al, 2015).…”

Section: Diarylheptanoids and Dietary Supplementsmentioning

confidence: 99%

Diarylheptanoids as nutraceutical: A review

Ganapathy

Preethi

Moses

et al. 2019

Biocatalysis and Agricultural Biotechnology

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Phenolic compounds are naturally occurring compounds present ubiquitously in plants. They have potential health benefits and substantiate evidence for their nutraceutical applications. Diarylheptanoids are part of the broad class of plant phenolics with structurally divergent compounds. They have been used in traditional medicines and homemade remedies to treat various ailments, as organoleptic additives in foods, and also for aesthetic purposes. With their potential therapeutic and organoleptic characteristics, diarylhepatanoids can be rightly termed as nutraceuticals. This review summarizes the wide range of pharmacological activities of diarylhepatanoids and nutraceutical formulations, with relevance to human health.

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Diarylheptanoids from lesser galangal suppress human colon cancer cell growth through modulating Wnt/β-catenin pathway

Cited by 20 publications

References 29 publications

A lignan induces lysosomal dependent degradation of FoxM1 protein to suppress β-catenin nuclear translocation

A lignan induces lysosomal dependent degradation of FoxM1 protein to suppress β-catenin nuclear translocation

Umbelliprenin isolated from Ferula sinkiangensis inhibits tumor growth and migration through the disturbance of Wnt signaling pathway in gastric cancer

Diarylheptanoids as nutraceutical: A review

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