Inhibitory effect of Erinacines A on the growth of DLD-1 colorectal cancer cells is induced by generation of reactive oxygen species and activation of p70S6K and p21

Lu, Chun‐Wei; Huang, Wen‐Shih; Lee, Kam-Fai; Lee, Ko‐Chao; Hsieh, Meng‐Che; Huang, Cheng-Yi; Lee, Li-Ya; Lee, Bih‐O; Teng, Chiao-Fang; Shen, Chien-Heng; Tung, Shui‐Yi; Kuo, Hsing‐Chun

doi:10.1016/j.jff.2015.12.031

Cited by 33 publications

(46 citation statements)

References 33 publications

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“…Normal hepatocytes were counted from 10 fields randomly chosen in liver samples from every group, using a 200× magnification light microscope. The mean values for normal cells were calculated per microscope field from six animals in each group [19]. …”

Section: Methodsmentioning

confidence: 99%

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Comparative Proteomic Identification of Protein Disulphide Isomerase A6 Associated with Tert-Butylhydroperoxide-Induced Liver Injury in Rat Hepatocytes

Shen

Tung

Huang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Oxidants are important human toxicants. They have been implicated in the occurrence and development of liver diseases. Increased intracellular tert-butylhydroperoxide (t-BHP) may be critical for oxidant toxicity, and is commonly used for evaluating mechanisms involving oxidative stress, but the method remains controversial. Methods: Primary cultures of hepatocytes as well as human Hep G2 and mouse FL83B liver cells were obtained. Cell viability was measured by annexin V–FITC/propidium iodide and DAPI staining to determine the effects of t-BHP treatment on acute liver injury. A proteomic assay provided information that was used to identify the differentially expressed proteins following t-BHP treatment; immunohistochemistry and western blotting were performed to detect the expression of PDIA6 activity in apoptotic and endoplasmic reticulum (ER) stress pathways. Results: Our results demonstrate that t-BHP treatment of liver cells increased cell cytotoxicity and the generation of reactive oxygen species. This treatment also increased the level of PDIA6; this was validated in vitro and in vivo based on a comparison of t-BHP-treated and -untreated groups. Treatment of mouse liver FL83B cells with t-BHP activated caspase 3, increased the expression of apoptotic molecules, caused cytochrome c release, and induced Bcl-2, Bax and IRE1α/TRAF2 complex formation. t-BHP-dependent induction of apoptosis was accompanied by sustained phosphorylation of the IRE1α/ASK1/JNK1/2/p38 pathways and PDIA6 expression. Furthermore, t-BHP induced liver FL83B cell viability and apoptosis by upregulating the levels of PDIA6; this process could be involved in the activation of the IRE1α/ASK1/JNK1/2/p38 signalling pathways. Conclusions: We conclude that t-BHP induced an apoptosis cascade and ER stress in hepatocytes by upregulation of PDIA6, providing a new mechanism underlying the effects of t-BHP on liver injury.

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Section: Methodsmentioning

confidence: 99%

“…The intracellular accumulation of ROS (O2-) was determined using the fluorescent probe H 2 DCFDA. The cells were washed prior to FACS analysis with the Cell Quest software (Becton Dickenson), as previously described [19]. The results are presented as a percentage of the fluorescent intensity compared with the control sample.…”

Section: Methodsmentioning

confidence: 99%

Comparative Proteomic Identification of Protein Disulphide Isomerase A6 Associated with Tert-Butylhydroperoxide-Induced Liver Injury in Rat Hepatocytes

Shen

Tung

Huang

et al. 2018

Cell Physiol Biochem

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“…The extracted ethanol solution was concentrated and fractionated by solvent partition between ethyl acetate and water to afford an H 2 O layer and an EtOAc layer. The EtOAc layer analysis was subjected to silica gel column chromatography according to the previous study [12, 13]; HPLC analysis of erinacine A was executed with minor modifications [12, 13]. The analytical column used was a COSMOSIL 5C18-AR-II (250 × 4.6 mm; particle size 5 µm, Nacalai USA, Inc., Kyoto, Japan).…”

Section: Methodsmentioning

confidence: 99%

“…1)-enriched H. erinaceous mycelia, which exhibit well-known anti-inflammatory and anticancer effects [10-13], have been extensively investigated and proposed to promote a decrease in cell viability and enhance apoptosis in various cancer cells. Moreover, our previous studies indicated that H. erinaceus mycelium and extracted erinacine A could be used to investigate the in vitro and in vivo antitumor activity through cell cycle arrest in the G1 phase of the human colorectal cancer cells involved in the generation of ROS and the activation of the p70S6K/NF-kB signaling pathway, which leads to p21 expression and inactivation of cdk2/cyclin E and cdk4/cyclin D1 [12]. However, little is known about the proliferation capacity, the invasiveness of gastric cancer cells, or the mechanism by which erinacine A inhibits cell growth, either by contributing to aggressiveness or cell death, which remains poorly understood.…”

Section: Introductionmentioning

confidence: 99%

“…Apoptosis can be activated as an important pathway under numerous extra- or intracellular stresses, such as starvation, reactive oxygen species (ROS), anticancer drug stimuli and phenolic phytochemicals [18, 19]. Recently, we identified that naturally produced erinacine A was reported to induce cell death in various cancer cell lines [12, 13] and plays roles in intracellular ROS production, where its levels are elevated in CRC and are sensitive to oxidative damage. It has been suggested that the reorganization of the actin cytoskeleton is a critical cellular response that influences the induction of apoptosis and modulates cell migration via FAK/AKT/p70S6K/ PAK1 kinases [13, 20].…”

Section: Introductionmentioning

confidence: 99%

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A Comparative Proteomic Analysis of Erinacine A’s Inhibition of Gastric Cancer Cell Viability and Invasiveness

Kuo

Lee

et al. 2017

Cell Physiol Biochem

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Background / Aims: Erinacine A, isolated from the ethanol extract of the Hericium erinaceus mycelium, has been demonstrated as a new alternative anticancer medicine. Drawing upon current research, this study presents an investigation of the molecular mechanism of erinacine A inhibition associated with gastric cancer cell growth. Methods: Cell viability was determined by Annexin V–FITC/propidium iodide staining and migration using a Boyden chamber assay to determine the effects of erinacine A treatment on the proliferation capacity and invasiveness of gastric cancer cells. A proteomic assay provided information that was used to identify the differentially-expressed proteins following erinacine A treatment, as well as the mechanism of its targets in the apoptotic induction of erinacine A. Results: Our results demonstrate that erinacine A treatment of TSGH 9201 cells increased cytotoxicity and the generation of reactive oxygen species (ROS), as well as decreased the invasiveness. Treatment of TSGH 9201 cells with erinacine A resulted in the activation of caspases and the expression of TRAIL. Erinacine A induction of apoptosis was accompanied by sustained phosphorylation of FAK/AKT/p70S6K and the PAK1 pathways, as well as the generation of ROS. Furthermore, the induction of apoptosis and anti-invasion properties by erinacine A could involve the differential expression of the 14-3-3 sigma protein (1433S) and microtubule-associated tumor suppressor candidate 2 (MTUS2), with the activation of the FAK/AKT/p70S6K and PAK1 signaling pathways. Conclusions: These results lead us to speculate that erinacine A may generate an apoptotic cascade in TSGH 9201 cells by activating the FAK/AKT/p70S6K/PAK1 pathway and upregulating proteins 1433S and MTUS2, providing a new mechanism underlying the anti-cancer effects of erinacine A in human gastric cancer cells.

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Secondary Metabolites from Higher Fungi

Chen

Liu

2017

Progress in the Chemistry of Organic Natural Products 106

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Secondary metabolites of higher fungi (mushrooms) are an underexplored resource compared to plant-derived secondary metabolites. An increasing interest in mushroom natural products has been noted in recent years. This chapter gives a comprehensive overview of the secondary metabolites from higher fungi, with 765 references highlighting the isolation, structure elucidation, biological activities, chemical syntheses, and biosynthesis of pigments, nitrogen-containing compounds, and terpenoids from mushrooms. Mushroom toxins are also included in each section.In a section on pigments of higher fungi, pigments are classified into four categories, namely, those from the shikimate-chorismate, acetate-malonate, and mevalonate biosynthetic pathways, and pigments containing nitrogen, with 145 references covering the years 2010-2016.In a section on other nitrogen-containing compounds of higher fungi, compounds are categorized primarily into nitrogen heterocycles, nucleosides, non-protein amino acids, cyclic peptides, and sphingolipids, with 65 references covering the years 2010-2016. In turn, in a section describing terpenoids of higher fungi, the sesquiterpenoids and diterpenoids are thoroughly elaborated, spanning the years 2001-2016, and 2009-2016, respectively. The divergent biosynthetic pathways from farnesyl pyrophosphate to sesquiterpenoids are also described. Selected triterpenoids with novel structures and promising biological activities, including lanostanes and ergostanes, are reported from the genus Ganoderma, and the fungi Antrodia cinnamomea and Poria cocos. In addition, cucurbitanes and saponaceolides are also compiled in this section.

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Inhibitory effect of Erinacines A on the growth of DLD-1 colorectal cancer cells is induced by generation of reactive oxygen species and activation of p70S6K and p21

Cited by 33 publications

References 33 publications

Comparative Proteomic Identification of Protein Disulphide Isomerase A6 Associated with Tert-Butylhydroperoxide-Induced Liver Injury in Rat Hepatocytes

Comparative Proteomic Identification of Protein Disulphide Isomerase A6 Associated with Tert-Butylhydroperoxide-Induced Liver Injury in Rat Hepatocytes

A Comparative Proteomic Analysis of Erinacine A’s Inhibition of Gastric Cancer Cell Viability and Invasiveness

Secondary Metabolites from Higher Fungi

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