Ergosterol peroxide from Chaga mushroom (Inonotus obliquus) exhibits anti-cancer activity by down-regulation of the β-catenin pathway in colorectal cancer

Kang, Ju‐Hee; Jang, Jeong-Eun; Mishra, Siddhartha; Lee, Hee-Ju; Nho, Chu Won; Shin, Dongyun; Jin, Myung; Kim, Mi Kyung; Choi, Changsun; Oh, Seung Hyun

doi:10.1016/j.jep.2015.07.030

Cited by 115 publications

(76 citation statements)

References 27 publications

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“…In the past decade, the effects of EP extracted from G. lucidum have been studied in various tumor types 9,11,26,27. The results of the present study indicate that EP suppresses β-catenin-induced transcription of Cyclin D1 and c-Myc in ovarian cancer cells.…”

Section: Discussionsupporting

confidence: 52%

Ergosterol peroxide inhibits ovarian cancer cell growth through multiple pathways

Tan¹,

Pan²,

Liu³

et al. 2017

OTT

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Ergosterol peroxide (EP), a sterol derived from medicinal mushrooms, has been reported to exert antitumor activity in several tumor types. However, the role of EP toward ovarian cancer cells has not been investigated. In this study, we analyzed the cytotoxicity of EP in various cell lines representing high-grade serous ovarian cancer and low-grade serous ovarian cancer, respectively. Although EP showed no significant inhibition of the viability of normal ovarian surface epithelial cells, it impaired the proliferation and invasion capacities of tumor cells in a dose-dependent manner. We further figured out key modulators involved in its antitumor effects by quantitative reverse transcription polymerase chain reaction, ELISA, and Western blot. The nuclear β-catenin was down-regulated upon EP treatment, subsequently reducing the Cyclin D1 and c-Myc expression levels. Meanwhile, the protein level of protein tyrosine phosphatase SHP2 was up-regulated in EP treated cells, whereas Src kinase activity was inhibited. Both activation of SHP2 phosphatase and inhibition of Src kinase decreased the phosphorylation level of transducer and activator of STAT3 protein, which was implicated in oncogenesis. On the other hand, EP remarkably inhibited the expression and secretion of VEGF-C, implying its involvement in counteracting tumor angiogenesis. Moreover, EP treatment showed comparable cytotoxic effect with β-catenin knock-down or STAT3 inhibition. Taken together, our results demonstrated that EP showed antitumor effects toward ovarian cancer cells through both β-catenin and STAT3 signaling pathways, making it a promising candidate for drug development.

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Section: Discussionsupporting

confidence: 52%

Ergosterol peroxide inhibits ovarian cancer cell growth through multiple pathways

Tan¹,

Pan²,

Liu³

et al. 2017

OTT

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“…Our results match with other previous reports describing the cytotoxic activity of ergosterol peroxide against colon (HCT-116, Caco-2) and HepG2 cell lines [18][19][20][21]. Recently, Kang et al [22] examined the effect of ergosterol peroxide on the viability of different colon cancer cells, and suggested that ergosterol peroxide downregulated b-catenin signaling, which exerted anti-proliferative and pro-apoptotic activities in colon cancer cells. However, the present study is the first to indicate the non-selectivity of ergosterol peroxide and its cytotoxicity to normal cell lines.…”

Section: Resultssupporting

confidence: 92%

Lucidumol C, a new cytotoxic lanostanoid triterpene from Ganoderma lingzhi against human cancer cells

et al. 2016

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A new oxygenated lanostane-type triterpene, named lucidumol C, together with six known compounds, was isolated from the chloroform extract of the fruiting bodies of Ganoderma lingzhi. Structures were established based on extensive spectroscopic and chemical studies. Potential cytotoxic activities of the isolated compounds were evaluated against human colorectal carcinoma (HCT-116, Caco-2), human liver carcinoma (HepG2), and human cervical carcinoma (HeLa) cell lines using WST-1 reagent. Selectivity was evaluated using normal human fibroblast cells (TIG-1 and HF19). Among the compounds, lucidumol C showed potent selective cytotoxicity against HCT-116 cells with an IC50 value of 7.86 ± 4.56 µM and selectivity index (SI) >10 with remarkable cytotoxic activities against Caco-2, HepG2 and HeLa cell lines.

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“…Furthermore, the aqueous extracts of I. obliquus inhibited the proliferation of colorectal cancer (Mishra et al, ), and the treatment of AOM/DSS mice with the same aqueous extracts inhibited the growth of colon tumor (Mishra et al, ). Additionally, in vitro studies in HCT116, HT‐29, SW620, and DLD‐1 colorectal cancer cell lines showed that ergosterol peroxide from I. obliquus suppressed the growth and formation of a clonogenic colony of colorectal cancer cells by reducing the levels of β‐catenin (Kang et al, ). Studies in the human colorectal carcinoma (HCT‐116) cell line further revealed that the extracts obtained by submerged fermentation from I. obliquus enhanced the apoptosis of cancerous colorectal cells, increased the expression levels of p53, and suppressed NF‐κB expression (Tsai, Li, & Lin, ).…”

Section: Inhibitory Effect Of I Obliquus Extracts On Tumor Growth Anmentioning

confidence: 99%

The pharmacological potential and possible molecular mechanisms of action of Inonotus obliquus from preclinical studies

Duru

Kovaleva

Данилова

et al. 2019

Phytotherapy Research

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The use of mushrooms as functional foods and in the treatment of diseases has a long history. Inonotus obliquus is a mushroom belonging to the Hymenochaetaceae family and has possible anticancer, antiviral, and hypoglycemic properties. Chemical analysis of this mushroom has allowed the identification of various constituents such as melanins, phenolic compounds, and lanostane-type triterpenoids. A plethora of findings have highlighted the potential molecular mechanisms of actions of this mushroom such as its ability to scavenge reactive oxygen species, inhibit the growth of tumors, decrease inflammation and insulin resistance in type 2 diabetes, and stimulate the immune system. This review summarizes the relevant findings with reference to the therapeutic potential of this mushroom in countering the progression of cancers, diabetes mellitus, and antiviral activities, while highlighting its possible molecular mechanisms of action. The possible role of this mushroom as a therapeutic agent in addressing the pathogenesis of diabetes and cancer has also been suggested.

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Ergosterol peroxide from Chaga mushroom (Inonotus obliquus) exhibits anti-cancer activity by down-regulation of the β-catenin pathway in colorectal cancer

Cited by 115 publications

References 27 publications

Ergosterol peroxide inhibits ovarian cancer cell growth through multiple pathways

Ergosterol peroxide inhibits ovarian cancer cell growth through multiple pathways

Lucidumol C, a new cytotoxic lanostanoid triterpene from Ganoderma lingzhi against human cancer cells

The pharmacological potential and possible molecular mechanisms of action of Inonotus obliquus from preclinical studies

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