Xanthohumol suppresses oestrogen-signalling in breast cancer through the inhibition of BIG3-PHB2 interactions

Yoshimaru, Tetsuro; Komatsu, Masato; Tashiro, Etsu; Imoto, Masaya; Osada, Hiroyuki; Miyoshi, Yasuo; Honda, Junko; Sasa, Mitsunori; Katagiri, Toyomasa

doi:10.1038/srep07355

Cited by 69 publications

(59 citation statements)

References 38 publications

(66 reference statements)

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“…Therefore, the identification of specific genes that are involved in the development of laryngeal squamous cell carcinoma may lead to further studies and the clinical application of gene therapy for laryngeal cancer. Previous studies have demonstrated that xanthohumol induces apoptosis in hepatocellular carcinoma (21), human cervical cancer cells (17) and breast cancer (22). To the best of our knowledge, the present study is the first to demonstrate that xanthohumol inhibits cell proliferation and induces cell apoptosis of laryngeal squamous cell carcinoma SCC4 cells.…”

Section: Discussionmentioning

confidence: 48%

Xanthohumol inhibits proliferation of laryngeal squamous cell carcinoma

Wang

Yin

et al. 2016

Oncology Letters

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Abstract. Xanthohumol is a flavonoid compound that exhibits antioxidant and anticancer effects, and is used to treat atherosclerosis. The aim of the present study was to investigate the effect of xanthohumol on the cell proliferation of laryngeal squamous cell carcinoma and to understand the mechanism of its action. The effects of xanthohumol on the cell viability and apoptosis rate of laryngeal squamous cell carcinoma SCC4 cells were assessed by Annexin V-fluorescein isothiocyanate/propidium iodide staining. In addition, the expression levels of pro-apoptotic proteins, caspase-3, caspase-8, caspase-9, poly ADP ribose polymerase (PARP) p53 and apoptosis-inducing factor (AIF), as well as anti-apoptotic markers, B-cell lymphoma 2 (Bcl-2) and myeloid cell leukemia 1 (Mcl-1), were analyzed by western blotting. The results revealed that treatment with 40 µM xanthohumol significantly inhibited the proliferation of SCC4 cells. Furthermore, xanthohumol treatment (40 µM) induced SCC4 cell apoptosis, as indicated by the significant increase in activity and expression of caspase-3, caspase-8, caspase-9, PARP, p53 and AIF. By contrast, the protein expression of Bcl-2 and Mcl-1 was significantly decreased following treatment with 40 µM xanthohumol. Taken together, the results of the present study indicated that xanthohumol mediates growth suppression and apoptosis induction, which was mediated via the suppression of Bcl-2 and Mcl-1 and activation of PARP, p53 and AIF signaling pathways. Therefore, future studies that investigate xanthohumol as a potential therapeutic agent for laryngeal squamous cell carcinoma are required.

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Section: Discussionmentioning

confidence: 48%

Xanthohumol inhibits proliferation of laryngeal squamous cell carcinoma

Wang

Yin

et al. 2016

Oncology Letters

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“…Since FOS is believed to have a pro-apoptotic function, loss of FOS leads to a more invasive and metastatic tumor phenotype [71]. PHB2 is a tumor suppressor that on activation has been shown to prevent the progression of ERα positive breast cancer [72]. Because of its anti-estrogenic effects, it abrogates the signaling of nuclear as well as membrane associated ERα [73].…”

Section: Discussionmentioning

confidence: 99%

Flaxseed and its components differentially affect estrogen targets in pre-neoplastic hen ovaries

Dikshit

Gao

Small

et al. 2016

The Journal of Steroid Biochemistry and Molecular Biology

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Flaxseed has been studied for decades for its health benefits that include anti-cancer, cardioprotective, anti-diabetic, anti-inflammatory properties. The biologically active components that mediate these effects are the omega-3 fatty acids and the lignan, secoisolaricirescinol diglucoside. We have previously shown that whole flaxseed supplemented diet decreases the severity and incidence of ovarian cancer while a 15% dose of flaxseed is most protective against inflammation and estrogen-induced chemical and genotoxicity. The objective of this study was to dissect the independent effects of the two flaxseed components on estrogen signaling and metabolism. Two and half year old hens were fed either a control diet, 15% whole flaxseed diet, defatted flax meal diet or 5% flax oil diet for 3 months after which the animals were sacrificed and blood and tissues were harvested. Whole flaxseed diet caused a decrease in expression of ERα. ERα target gene expression was assessed using RT2 profiler PCR array. Some targets involved in the IGF/insulin signaling pathway (IRS1, IGFBP4, IGFBP5) were downregulated by flaxseed and its components. Flaxseed diet also downregulated AKT expression. A number of targets related to NF-κB signaling were altered by flaxseed diet including a series of targets implicated in cancer. Whole flaxseed diet also affected E2 metabolism by increasing CYP1A1 expression with a corresponding increase in the onco-protective E2 metabolite, 2-methoxyestradiol. The weak anti-estrogens, enterolactone, enterodiol and 2-methoxyestradiol, might be working synergistically to generate a protective effect on the ovaries from hens on whole flaxseed diet by altering the estrogen signaling and metabolism.

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“…Its constituent 8-PN is considered the most potent phytoestrogen isolated to date and binds to ERα and ERβ (Milligan et al 2002, Busch et al 2015. XAN is less potent than 8-PN, and is known to exhibit anti-carcinogenic properties and to prevent initiation and progression of cancer (Gerhauser et al 2002, Deeb et al 2010, Yoshimaru et al 2014. XAN seems to inhibit the proliferation of ERα-positive breast cancer cells through suppression of the E2-signalling pathways , Yoshimaru et al 2014.…”

Section: Introductionmentioning

confidence: 99%

“…XAN is less potent than 8-PN, and is known to exhibit anti-carcinogenic properties and to prevent initiation and progression of cancer (Gerhauser et al 2002, Deeb et al 2010, Yoshimaru et al 2014. XAN seems to inhibit the proliferation of ERα-positive breast cancer cells through suppression of the E2-signalling pathways , Yoshimaru et al 2014. COU is a representative of the coumestan group which naturally occurs in broccoli (Brassica oleracea L.), red clover sprouts, alfalfa sprouts (Medicago sativa L.), and soy beans (Adams 1995, Harris et al 2005.…”

Section: Introductionmentioning

confidence: 99%

Interactions between plant-derived oestrogenic substances and the mycoestrogen zearalenone in a bioassay with MCF-7 cells

Hessenberger¹,

Botzi²,

Degrassi³

et al. 2017

Polish Journal of Veterinary Sciences

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Human and animal diets may contain several non-steroidal oestrogenic compounds which originate either from plants (phytoestrogens) or from fungi that infect plants (mycoestrogens such as zearalenone (ZEN)). Phytoestrogens may compete with ZEN in binding to the oestrogen receptor β and thereby may counteract the oestrogenic activity of ZEN. Using a modified version of the E-screen assay, plant-derived oestrogenic substances were tested for their proliferative or anti-proliferative effect on oestrogen-dependent MCF-7 cells. The samples were additionally tested for their ability to influence the oestrogenic activity of ZEN (1 μM). Among the individual substances tested, 8-prenylnaringenin had the strongest effect, as cell proliferation was increased by 78% at the lowest concentration (0.23 μM), and by 167% at the highest concentration (29.4 μM). Coumestrol (5.83 μM) increased cell proliferation by 39%, and genistein (370 μM) by 61%, respectively. Xanthohumol and enterolactone did not stimulate cell proliferation significantly. In the co-incubation experiments with ZEN, none of the single substances was able to decrease the oestrogenic activity of ZEN. Only for 8-prenylnaringenin (14.7 and 29.4 μM) was a trend towards an increase in the ZEN-induced cell proliferation up to 72% observed. In conclusion, with the exception of 8-prenylnaringenin, no substantial interaction between phytoestrogens and the mycotoxin ZEN could be detected using a bioassays with MCF-7 cells.

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Xanthohumol suppresses oestrogen-signalling in breast cancer through the inhibition of BIG3-PHB2 interactions

Cited by 69 publications

References 38 publications

Xanthohumol inhibits proliferation of laryngeal squamous cell carcinoma

Xanthohumol inhibits proliferation of laryngeal squamous cell carcinoma

Flaxseed and its components differentially affect estrogen targets in pre-neoplastic hen ovaries

Interactions between plant-derived oestrogenic substances and the mycoestrogen zearalenone in a bioassay with MCF-7 cells

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