Ergosterol peroxide activates Foxo3-mediated cell death signaling by inhibiting AKT and c-Myc in human hepatocellular carcinoma cells

Li, Xiangmin; Wu, Qingping; Bu, Ming; Hu, Liming; Du, William W.; Jiao, Chunwei; Pan, Honghui; Sdiri, Mouna; Wu, Nan; Xie, Yizhen; Yang, Burton B.

doi:10.18632/oncotarget.8608

Cited by 59 publications

(43 citation statements)

References 42 publications

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“…One of the reasons for lack of clinical perspective studies is the complicated components in medicinal mushrooms, and the isolation and purification of EP is not easy. However, Li et al recently reported the chemical synthesis of EP, which possesses a comparable antitumor effect to G. lucidum extracts 13. The successful synthesis makes it possible for further animal and clinical studies to verify the specific antitumor effects of EP.…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

Ergosterol peroxide inhibits ovarian cancer cell growth through multiple pathways

Tan¹,

Pan²,

Liu³

et al. 2017

OTT

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“…Human HepG2 cells (a kind gift from the Harbin Medical University Cancer Institute) were cultured as previously described [32], in RPMI 1640 medium (HyClone, USA) supplemented with 10% foetal bovine serum (GIBCO, USA), 100 IU/ml penicillin and 100 g/ml streptomycin. The cells were cultured at 37 ℃ in a 5% CO 2 environment.…”

Section: Cell Culture and Treatmentsmentioning

confidence: 99%

Glucagon-Like Peptide-1 Modulates Cholesterol Homeostasis by Suppressing the miR-19b-Induced Downregulation of ABCA1

Yao¹,

Li²,

Wang³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Abnormal regulation of cholesterol homeostasis is associated with type 2 diabetes mellitus (T2DM) and multiple other diseases. Glucagon-like peptide-1 (GLP-1) has unique effects on modulating hepatic lipid metabolism. However, the mechanism behind these is largely unknown. The aim of this study was to investigate the effects of GLP-1 on cholesterol-induced lipotoxicity in hepatocytes and examine the underlying mechanisms. Methods: Cell viability was determined by CCK-8. Caspase-3 detection was used to assess the effects of GLP-1 on cholesterol-induced apoptosis. TNF-α and IL-6 as the inflammatory markers were measured by ELISA. The alterations of miR-19b and ATP-binding cassette transporter A1 (ABCA1) resulting from high-fat diet/cholesterol incubation or GLP-1 were detected by real-time PCR and western blot. Results: GLP-1 markedly up-regulated the expression of ABCA1 protein, but didn’t affect peroxisome proliferator-activated receptor α (PPAR-α) protein. The miR-19b levels were significantly down-regulated in GLP-1-treated groups. The inhibition and overexpression of miR-19b were established to explore the effects of a GLP-1-mediated alteration in miR-19b. Cholesterol transport assays revealed that treatment with GLP-1 alone or together with miR-19b inhibitor significantly enhanced ABCA1-dependent cholesterol efflux, resulting in reduced total cholesterol. Further, histological examination was used to detect lipid accumulation. Cholesterol significantly attenuated cell viability, promoted hepatic cell apoptosis, and facilitated lipid accumulation, and these effects could be reversed by GLP-1. Conclusion: GLP-1 may affect cholesterol homeostasis by regulating the expression of miR-19b and ABCA1.

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“…Ergosterol peroxide (5α,8α-epidioxiergosta-6,22-dien-3β-ol, EP) is a member of a class of fungal secondary metaboliters of sterol 5α,8α-endoperoxidederivatives ( Figure 2). A number of biological activities have been attributed to EP, including antitumor, anti-inflammatory, antiviral and immunomodulatory activities and antioxidant activities [16][17][18][19][20][21]. As an important active lead compound in drug discovery, EP is well known for its 5α,8α-peroxy moiety.…”

Section: Introductionmentioning

confidence: 99%

Novel Steroidal 5α,8α-Endoperoxide Derivatives with Semicarbazone/Thiosemicarbazone Side-chain as Apoptotic Inducers through an Intrinsic Apoptosis Pathway: Design, Synthesis and Biological Studies

Wang

et al. 2020

Molecules

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A series of novel steroidal 5α,8α-endoperoxide derivatives bearing semicarbazone (7a–g) or thiosemicarbazone (7h–k) side chain were designed, synthesized and evaluated for their cytotoxicities in four human cancer cell lines (HepG2, HCT-116, MCF-7, and A549) using the MTT assay in vitro. The results showed that compound 7j exhibited significant cytotoxic activity against HepG2 cells (IC50 = 3.52 μM), being more potent than ergosterol peroxide. Further cellular mechanism studies in HepG2 cells indicated that compound 7j triggered the mitochondrial-mediated apoptosis by decreasing mitochondrial membrane potential (MMP), which was associated with up-regulation of Bax, down-regulation of Bcl-2, activation levels of the caspase cascade, and formation of reactive oxygen species (ROS). The above findings indicated that compound 7j may be used as a promising skeleton for antitumor agents with improved efficacy.

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Ergosterol peroxide activates Foxo3-mediated cell death signaling by inhibiting AKT and c-Myc in human hepatocellular carcinoma cells

Cited by 59 publications

References 42 publications

Ergosterol peroxide inhibits ovarian cancer cell growth through multiple pathways

Ergosterol peroxide inhibits ovarian cancer cell growth through multiple pathways

Glucagon-Like Peptide-1 Modulates Cholesterol Homeostasis by Suppressing the miR-19b-Induced Downregulation of ABCA1

Novel Steroidal 5α,8α-Endoperoxide Derivatives with Semicarbazone/Thiosemicarbazone Side-chain as Apoptotic Inducers through an Intrinsic Apoptosis Pathway: Design, Synthesis and Biological Studies

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