The coffee diterpene kahweol suppresses the cell proliferation by inducing cyclin D1 proteasomal degradation via ERK1/2, JNK and GKS3β-dependent threonine-286 phosphorylation in human colorectal cancer cells

Park, Gwang Hun; Song, Hun Min; Jeong, Jin Boo

doi:10.1016/j.fct.2016.07.008

Cited by 33 publications

(23 citation statements)

References 45 publications

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“…NF-κB activation has been found in many human cancers, which plays important roles in cancer proliferation, invasion and metastasis and associates with poor survival rate ( 19 – 21 ). cyclin D1 and cyclin E play pivotal roles in cell growth of many malignant cancers ( 22 , 23 ). NF-κB could upregulate its downstream molecule cyclin D1 through phosphorylation of p65 and IκB, which induced NF-κB p65 nuclear localization and subsequent transcriptional activation of cyclin related proteins ( 24 ).…”

Section: Discussionmentioning

confidence: 99%

Chrysophanol inhibits proliferation and induces apoptosis through NF-κB/cyclin D1 and NF-κB/Bcl-2 signaling cascade in breast cancer cell lines

Ren

Dai

et al. 2018

Mol Med Report

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Chrysophanol is an anthraquinone compound, which exhibits anticancer effects on certain types of cancer cells. However, the effects of chrysophanol on human breast cancer remain to be elucidated. The aim of the present study was to clarify the role of chrysophanol on breast cancer cell lines MCF-7 and MDA-MB-231, and to identify the signal transduction pathways regulated by chrysophanol. MTT assay and flow cytometric analysis demonstrated that chrysophanol inhibited cell proliferation, and cell cycle progression in a dose-dependent manner. The expression of cell cycle-associated cyclin D1 and cyclin E were downregulated while p27 expression was upregulated following chrysophanol treatment at the mRNA, and protein levels. The Annexin V/propidium iodide staining assay results revealed that apoptosis levels increased following chrysophanol treatment. Chrysophanol upregulated caspase 3 and poly (ADP-ribose) polymerase cleavage in both cell lines. Furthermore, chrysophanol enhanced the effect of paclitaxel on breast cancer cell apoptosis. In addition, chrysophanol downregulated apoptosis regulator Bcl-2 protein, and transcription factor p65 and IκB phosphorylation. Inhbition of nuclear factor (NF)-κB by ammonium pyrrolidine dithiocarbamate diminished the effect of chrysophanol on apoptosis and associated proteins. In conclusion, the results of the current study demonstrated that chrysophanol effectively suppresses breast cancer cell proliferation and facilitates chemosentivity through modulation of the NF-κB signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Chrysophanol inhibits proliferation and induces apoptosis through NF-κB/cyclin D1 and NF-κB/Bcl-2 signaling cascade in breast cancer cell lines

Ren

Dai

et al. 2018

Mol Med Report

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“…Many studies on kahweol have defined its inhibitory effects on cancer, angiogenesis, and inflammation. For example, kahweol inhibits cell growth by inducing proteasomal degradation of cyclin D1 via ERK1/2, JNK, and GKS3β-dependent phosphorylation ( 22 ) and HSP 70 Expression ( 23 ) in human colorectal cancer. Kahweol induces apoptosis via inhibition of STAT3 phosphorylation in human lung adenocarcinoma A549 cells ( 24 ).…”

Section: Discussionmentioning

confidence: 99%

Kahweol inhibits lipid accumulation and induces Glucose-uptake through activation of AMP-activated protein kinase (AMPK)

et al. 2017

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Weight loss ≥ 5 percent is sufficient to significantly reduce health risks for obese people; therefore, development of novel weight loss compounds with reduced toxicity is urgently required. After screening of natural compounds with anti-adipogenesis properties in 3T3-L1 cells, we determined that kahweol, a coffee-specific diterpene, inhibited adipogenesis. Kahweol reduced lipid accumulation and expression levels of adipogenesis and lipid accumulation-related factors. Levels of phosphorylated AKT and phosphorylated JAK2, that induce lipid accumulation, decreased in kahweol-treated cells. Particularly, kahweol treatment significantly increased AMP-activated protein kinase (AMPK) activation. We revealed that depletion of AMPK alleviated reduction in lipid accumulation from kahweol treatment, suggesting that inhibition of lipid accumulation by kahweol is dependent on AMPK activation. We detected more rapid reduction in blood glucose levels in mice administrated kahweol than in control mice. We suggest that kahweol has anti-obesity effects and should be studied further for possible therapeutic applications.

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“…The viability of cells pretreated with HSP 70 inhibitor triptolide and treated with kahweol was significantly lower than the viability of those treated with kahweol only. The impact of kahweol on human colorectal cancer cells HCT116 and SW480, and on human colon normal cells CCD-18C0, was also assessed by Park et al [181]. The cells were treated with different concentrations of kahweol, up to 50 μM.…”

Section: Kahweolmentioning

confidence: 99%

The Impact of Coffee and Its Selected Bioactive Compounds on the Development and Progression of Colorectal Cancer In Vivo and In Vitro

et al. 2018

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Coffee is one of the most popular beverages worldwide. Coffee contains bioactive compounds that affect the human body such as caffeine, caffeic acid, chlorogenic acids, trigonelline, diterpenes, and melanoidins. Some of them have demonstrated potential anticarcinogenic effects in animal models and in human cell cultures, and may play a protective role against colorectal cancer. Colorectal cancer (CRC) is the third leading cause of cancer-related mortality in the USA and other countries. Dietary patterns, as well as the consumption of beverages, may reduce the risk of CRC incidence. In this review, we focus on published epidemiological studies concerning the association of coffee consumption and the risk of development of colorectal cancer, and provide a description of selected biologically active compounds in coffee that have been investigated as potential cancer-combating compounds: Caffeine, caffeic acid (CA), chlorogenic acids (CGAs), and kahweol in relation to colorectal cancer progression in in vitro settings. We review the impact of these substances on proliferation, viability, invasiveness, and metastasis, as well as on susceptibility to chemo- and radiotherapy of colorectal cancer cell lines cultured in vitro.

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The coffee diterpene kahweol suppresses the cell proliferation by inducing cyclin D1 proteasomal degradation via ERK1/2, JNK and GKS3β-dependent threonine-286 phosphorylation in human colorectal cancer cells

Cited by 33 publications

References 45 publications

Chrysophanol inhibits proliferation and induces apoptosis through NF-κB/cyclin D1 and NF-κB/Bcl-2 signaling cascade in breast cancer cell lines

Chrysophanol inhibits proliferation and induces apoptosis through NF-κB/cyclin D1 and NF-κB/Bcl-2 signaling cascade in breast cancer cell lines

Kahweol inhibits lipid accumulation and induces Glucose-uptake through activation of AMP-activated protein kinase (AMPK)

The Impact of Coffee and Its Selected Bioactive Compounds on the Development and Progression of Colorectal Cancer In Vivo and In Vitro

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