學術論文


Academic papers

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論文出處:J Ethnopharmacol. 2021 Mar 25;268:113570. doi: 10.1016/j.jep.2020.113570.

論文名稱:Antrodia camphorata extract (ACE)-induced apoptosis is associated with BMP4 expression and p53-dependent ROS generation in human colon cancer cells.

作  者:Ding R, Ning X, Ye M, Yin Y.

出 版 年:2021

分  類:抗癌

論文結論:Ethnopharmacological relevance
Antrodia camphorata (AC) is a rare functional fungus in Taiwan and is known as traditional Chinese medicine. It has been reported to inhibit proliferation and promote apoptosis in human cancer cells.
Aim of the study: To investigate the potential mechanism of apoptosis induced in colon cancer cells by Antrodia camphorata extract (ACE).
Materials and methods
The MTT assay and crystal violet staining were used to determine relative cell viability in vitro at 24 and 48 h. The effects of ACE on apoptosis were determined by Hoechst 33342 staining and flow cytometric analysis following Annexin V-FITC/PI staining. The gene expression profile of HCT116 cells was assessed by the RNA sequencing system. In combination with RNA-seq data and qRT-PCR, Western blot analysis was used to evaluate expression of proteins. The intracellular ROS of HCT116 cells were determined using a DCFH-DA fluorescence probe.
Results
ACE significantly reduces cell viability in a dose-dependent manner and triggers apoptosis. To explore the underlying mechanism, we performed transcriptome analysis of ACE-treated colon cancer HCT116 cells. Bioinformatics analyses showed that ACE treatment is associated with pathways in cancer. We further used Cytoscape to analyze hub genes in this network. Among them, BMP4, which is associated with cancer cell death through regulation of the tumor suppressor p53, was significantly decreased at both mRNA and protein levels in ACE treatment groups. We found that cell death is reversible via inactivation or knockdown of p53 gene and reduction of reactive oxygen species (ROS) generation in response to ACE exposure, indicating that p53 plays an important role in ROS generation induced by ACE. Meanwhile, ROS scavenger NAC was used to verify that cell death is reversible via reduction of ROS.
Conclusion
Our findings demonstrate that ACE has potential as an anticancer agent that induces apoptosis through BMP4 and p53-dependent response to ROS in human colon cancer.
 

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論文出處:Plants (Basel). 2021 Apr 9;10(4):737. doi: 10.3390/plants10040737.

論文名稱:Identification and Isolation of an Intermediate Metabolite with Dual Antioxidant and Anti-Proliferative Activity Present in the Fungus Antrodia cinnamomea Cultured on an Alternative Medium with Cinnamomum kanehirai Leaf Extract.

作  者:Zeng WW, Chen TC, Liu CH, Wang SY, Shaw JF, Chen YT.

出 版 年:2021

分  類:抗癌

論文結論:The fungus Antrodia cinnamomea has been used as a folk medicine for various diseases, especially cancer. When A. cinnamomea is cultured on the original host, an endangered woody plant Cinnamomum kanehirai Hayata, the fungus produces more active ingredients, but its growth is slow. Here, C. kanehirai leaf ethanol extract (KLEE) was used as a substitute for C. kanehirai wood to culture A. cinnamomea on solid medium to shorten the culture period and produce active metabolites en masse. The antioxidant activities of methanol extracts from A. cinnamomea cultured on KLEE (MEAC-KLEE) were evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging effect, reducing power, and ferrous ion-chelating effect, and the effective concentration (EC50) values were 0.27, 0.74, and 0.37 mg mL−1, respectively. MEAC-KLEE exhibited specific anti-proliferative activity against a non-small-cell lung cancer cell line (A549) by Annexin V assay. A secondary metabolite (2,4-dimethoxy-6-methylbenzene-1,3-diol, DMMB) present in the extract (MEAC-KLEE) was purified by high-performance liquid chromatography (HPLC) and identified by nuclear magnetic resonance (NMR) spectra. DMMB exhibited moderate antioxidant activity against DPPH radicals and reducing power, with EC50 values of 12.97 and 25.59 μg mL−1, respectively, and also induced apoptosis in A549 cells. Our results provide valuable insight into the development of DMMB for nutraceutical biotechnology.

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論文出處:Am J Chin Med. 2021;49(4):983-999. doi: 10.1142/S0192415X21500476.

論文名稱:4-Acetylantrocamol LT3 Inhibits Glioblastoma Cell Growth and Downregulates DNA Repair Enzyme O6-Methylguanine-DNA Methyltransferase.

作  者:Lee SY, Yen IC, Lin JC, Chung MC, Liu WH.

出 版 年:2021

分  類:抗癌

論文結論:Glioblastoma multiforme (GBM) is a deadly malignant brain tumor that is resistant to most clinical treatments. Novel therapeutic agents that are effective against GBM are required. Antrodia cinnamomea has shown antiproliferative effects in GBM cells. However, the exact mechanisms and bioactive components remain unclear. Thus, the present study aimed to investigate the effect and mechanism of 4-acetylantrocamol LT3 (4AALT3), a new ubiquinone from Antrodia cinnamomeamycelium, in vitro. U87 and U251 cell lines were treated with the indicated concentration of 4AALT3. Cell viability, cell colony-forming ability, migration, and the expression of proteins in well-known signaling pathways involved in the malignant properties of glioblastoma were then analyzed by CCK-8, colony formation, wound healing, and western blotting assays, respectively. We found that 4AALT3 significantly decreased cell viability, colony formation, and cell migration in both in vitro models. The epidermal growth factor receptor (EGFR), phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR), Hippo/yes-associated protein (YAP), and cAMP-response element binding protein (CREB) pathways were suppressed by 4AALT3. Moreover, 4AALT3 decreased the level of DNA repair enzyme O6-methylguanine-DNA methyltransferase and showed a synergistic effect with temozolomide. Our findings provide the basis for exploring the beneficial effect of 4AALT3 on GBM in vivo.
 

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論文出處:Int J Biol Macromol. 2021 Feb 15;170:307-316. doi: 10.1016/j.ijbiomac.2020.12.135.

論文名稱:Structural sequencing and anti-inflammatory, anti-lung cancer activities of 1,4-alpha/beta-sulfomalonoglucan in Antrodia cinnamomea.

作  者:Lu MK, Chao CH, Hsu YC, Chang CC.

出 版 年:2020

分  類:抗癌

論文結論:Antrodia cinnamomea is a precious Polyporaceous fungus with various bioactivities. This study reports the chemical identification and biological activities of sulfomalonoglucan, a sulfated polysaccharide (SPS), from the sodium sulfate enriched medium of the title fungus. The SPS-containing fraction was separated by gel filtration chromatography (GFC) to give the title SPS (denoted as Na10_SPS-F3). By analyzing the evidence for key inter-glycosidic linkages in the 1D and 2D NMR spectroscopic data, one possible repeat unit was proposed as: Na10_SPS-F3 inhibited the secretion of tumor necrosis factor (TNF-α) and interleukin (IL)-6 after lipopolysaccharide (LPS) stimulation in RAW264.7 macrophages. Mechanistically, Na10_SPS-F3 downregulated TGFRII also attenuated the LPS-induced IκB-α degradation. Moreover, Na10_SPS-F3 inhibited lung cancer cell H1975 EGFR/ERK signaling. This is the first paper reporting a 3-O-sulfomalonyl glucan (Na10_SPS-F3) with eight 1,4-β-Glc moieties connected with ten 1,4-α-Glc moieties from Antrodia cinnamomea and its anti-inflammatory and anti-cancer activities.

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論文出處:J Cosmet Dermatol. 2020 Nov 17. doi: 10.1111/jocd.13847.

論文名稱:Extracts of Antrodia cinnamomea mycelium as a highly potent tyrosinase inhibitor. 

作  者:Chen HY, Cheng KC, Wang HT, Hsieh CW, Lai YJ.

出 版 年:2020

分  類:抗癌

論文結論:
Background
Ganoderma has been known as a cure for diseases since ancient times, and been used as a medicinal mushroom for more than 2000 years. By many accounts, Ganoderma lucidum extracts from fruit bodies exhibited the comparable tyrosinase inhibition activity.
Aims
To validate A. cinnamomea mycelia anti-melanogenesis activity. Ethanolic extracts of A. cinnamomea mycelia were evaluated using in vitro cell-free tyrosinase assay, cell-based and zebrafish phenotype-based method. Meanwhile, safety assessment was also conducted to ensure the feasibility as the novel ingredients in cosmetic and pharmaceutic industries.
Methods
The major regulatory enzymes being in charge of cutaneous pigmentation, was investigated in both cell-free and cellular enzyme systems, and in phenotype-based zebrafish model. A high-throughput TLC in vitro screening system was introduced to perform the initial evaluation of those with anti-melanin formation activity.
Results
Among the fractions, 50% ethanol extracted fraction (AC_Et50_Hex) exhibited highest anti-melanin formation activity. AC_Et50_Hex (at 100 ppm) reduced 30% intracellular melanin of B16-F10 cells through suppression of tyrosinase activity and its protein expression. For animal study, not only does AC_Et50_Hex exhibited similar depigmenting efficacy to kojic acid (56.1% vs 52.3%) with lower dosage (50 ppm vs 1400 ppm), but showed less toxicity to zebrafish.
Conclusion
A. cinnamomea mycelium extracts can be an ideal candidate/substitute for skin-whitening since kojic acid has been reported with carcinogenic effect. AC_Et50_Hex was recognized as a potential tyrosinase inhibitor throughout in vitro and in vivo analysis studies. The mass production of A. cinnamomea mycelium from agitated fermentation realizes the natural mushroom extracts for commercial application.

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論文出處:Int J Biol Macromol. 2020 Nov 1;162:1476-1483. doi:10.1016/j.ijbiomac.2020.07.201.

論文名稱:Effects of sterol-type elicitors on biochemical characterization of polysaccharides from Antrodia cinnamomea.

作  者:Lin TY, Lu MK, Tseng AJ, Chao CH.

出 版 年:2020

分  類:抗癌

論文結論:Sterols play crucial roles in the physiological functions of organisms. In this study, we examined the chemical and biological effects of sterol type elicitors, including squalene, cholesterol and stigmasterol, on polysaccharides (PSs) of Antrodia cinnamomea. Characteristic studies revealed that squalene and stigmasterol effectively increased the glucose contents in PSs. Specifically, squalene not only induced glucose content but also increased fucose and mannose levels in PSs. However, cholesterol did not induce changes in sugar content in PSs. We further identified that high dose squalene significantly promoted 20% yield (w/w) of PSs as well as significantly increased the glucose, galactose and fucose contents. In addition, the major PSs species had a molecular weight of 21 kDa, and squalene significantly increased its area percentage to 43.54. The biological effects of PSs (squalenePS) from squalene treated A. cinnamomea presented anticancer activities by inhibiting lung cancer cell viability and colony formation. Functional studies revealed that squalenePS reduced the glucose uptake and lactate secretion may correlate to inhibition of AKT activity and downregulation of glucose transporter (GLUT1) expression. Our findings suggested squalene may play vital roles in regulating the PSs assembling and bioactivities of A. cinnamomea. Moreover, squalene may be a potential supplement for adding the culture medium of A. cinnamomea.

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論文出處:J Pharm Biomed Anal. 2020 Aug 5;187:113142. doi: 10.1016/j.jpba.2020.113142.

論文名稱:Proteomic analysis of Antrodia Cinnamomea-induced ER stress
in liver cancer cells.

作  者:Chen JF, Tsai YT, Lai YH, Lin CC, Chou HC, Kuo WH, Ko ML, Wei YS, Wang YS, Lin MW, Chen YJ, Lee YR, Chan HL.

出 版 年:2020

分  類:抗癌

論文結論:Antrodia Cinnamomea is a fungus species widely used as a herb medicine for hypertension, cancer and handover. Nevertheless, the biological roles of Antrodia Cinnamomea on the molecular mechanism of liver cancer are not entirely understood. To determine whether Antrodia Cinnamomea is able to be used for the treatment of liver cancer and its molecular mechanism, we examined the effect of Antrodia Cinnamomea on the differential proteomic patterns in liver cancer cell lines HepG2 and C3A as well as in Chang’s liver cell, a normal liver cell, using quantitative proteomic approach. The proteomic analysis demonstrated that abundance of 82, 125 and 125 proteins was significantly altered in Chang’s liver cells, C3A and HepG2, respectively. The experimental outcomes also demonstrated that Antrodia Cinnamomea-induced cytotoxicity in liver cancer cells mostly involved dysregulation of protein folding, cytoskeleton regulation, redox-regulation, glycolysis pathway as well as transcription regulation. Further analysis also revealed that Antrodia Cinnamomea promoted misfolding of intracellular proteins and dysregulate of cellular redox-balance resulting in ER-stress. To sum up our studies demonstrated that the proteomic strategy used in this study offered a tool to investigate the molecular mechanisms of Antrodia Cinnamomea-induced liver cancer cytotoxicity. The proteomic results might be further evaluated as prospective targets in liver cancer treatment.

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論文出處:Medicine (Baltimore). 2020 Jul 2;99(27):e20808. doi: 10.1097/MD.0000000000020808.

論文名稱:Antrodia cinnamomea is a potentially effective complementary medicine for adjuvant therapy against breast cancer with bone metastasis: A case report.

作  者:Long H, Hu CT, Prijatelj V, Weng CF.

出 版 年:2020

分  類:抗癌

論文結論:Rationale: 
Palbociclib (PAL) is a first-in-class selective inhibitor of the cyclin-dependent kinases 4 (CDK4) and CDK6 and is indicated for the treatment of hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) in combination with fulvestrant (FUL) in postmenopausal women. Antrodia cinnamomea (AC), a well-known Chinese folk medicine in Taiwan, possesses numerous biological capabilities, most notably an anti-tumor effect. However, the clinical use of AC as complementary medicine combined with adjuvant therapy is unexplored. In this case report, we evaluated AC combined with PAL plus FUL to reduce the tumor burden in an MBC patient.
Patient concerns: 
A Slovenian woman diagnosed with relapsed bone metastases of breast cancer (BC) was unable to undergo surgery and refused radiation therapy due to fear of side effects; she also feared the side effects of adjuvants. However, she was eager to live with a high quality of life.
Diagnosis: 
Stage IV, HR-positive/HER2-negative BC with relapse of bone metastases.
Interventions: 
After diagnosis of relapse of bone metastases, she received adjuvant with PAL plus FUL. Additionally, she chose to take AC orally (10 g/d).
Outcomes: 
The pain was mostly relieved, and the side effects of adjuvant therapy reduced. Magnetic resonance imaging revealed reduction of tumor size at the fifth month of adjuvant therapy plus AC. After 14 months of adjuvant therapy plus AC, the tumors at the thoracic vertebrae T1 and T3 were found to have shrunk from 35.2 and 12.0 mm to 28.1 and 9.9 mm, respectively. Remarkably, no further metastases were observed.
Lessons: 
According to the circulating tumor cells (CTCs) test data, AC had better anti-tumor efficacy on active tumor cells than PAL plus FUL. Thus, AC could be an effective complementary medicine for adjuvant therapy in patients with HR-positive/HER2-negative MBC. Interestingly, continued elevation of carcinoma antigen 15-3 and lactate dehydrogenase levels but decreasing levels of alkaline phosphatase were observed, which may be indicative of the potent efficacy of treatment resulting in massive tumor cell death. The CTCs test may be a sensitive approach to monitor the progression of BC and subsequently evaluate the efficiency of therapy.

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論文出處:Int J Mol Sci. 2019 Feb 15;20(4). pii: E833. doi: 10.3390/ijms20040833.

論文名稱:Antrodia cinnamomea, a Treasured Medicinal Mushroom, Induces Growth Arrest in Breast Cancer Cells, T47D Cells: New Mechanisms Emerge.

作  者:Chen YC, Liu YC, El-Shazly M, Wu TY, Chang JG, Wu YC.

出 版 年:2019

分  類:抗癌

論文結論:Ethanol extract of artificially cultured Antrodia cinnamomea (EEAC) inhibited breast cancer cells (T47D cells) proliferation mediated by cell cycle arrest at G1 phase as well induced autophagy. EEAC not only decreased the expression of the cell-cycle-related proteins but also increased the expression of transcription factor FOXO1, autophagic marker LC3 II, and p62. EEAC mediated endoplasmic reticulum stress by promoting the expression of IRE1 (inositol-requiring enzyme 1α), GRP78/Bip (glucose regulating protein 78), and CHOP (C/EBP homologous protein).

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論文出處:Phytomedicine. 2019 Jan;52:70-78. doi: 10.1016/j.phymed.2018.09.213. Epub 2018 Sep 27.

論文名稱:Antrocin, a bioactive component from Antrodia cinnamomea, suppresses breast carcinogenesis and stemness via downregulation of β-catenin/Notch1/Akt signaling.

作  者:Chen JH, T H Wu A, T W Tzeng D, Huang CC, Tzeng YM, Chao TY.

出 版 年:2019

分  類:抗癌

論文結論:Antrocin, an active component of Antrodia cinnamomea, treatment suppressed the viability, migration colony formation and mammosphere generation. Antrocin-mediated anti-cancer effects were associated with the decreased expression of oncogenic and stemness markers such as β-catenin, Akt and Notch1.

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論文出處:J Cell Physiol. 2019 Apr;234(4):4125-4139. doi: 10.1002/jcp.27222. Epub 2018 Aug 26.

論文名稱:Antrodia camphorata inhibits epithelial-to-mesenchymal transition by targeting multiple pathways in triple-negative breast cancers.

作  者:Hseu YC, Chang GR, Pan JY, Rajendran P, Mathew DC, Li ML, Liao JW, Chen WT, Yang HL

出 版 年:2019

分  類:抗癌

論文結論:

The fermented Antrodia camphorata (AC) exhibits potential for engendering cell-cycle arrest as well as prompting apoptosis and metastasis inhibition in triple-negative breast cancer (TNBC) cells.
1. Rversed the morphological changes (fibroblastic-to-epithelial phenotype) as well as the EMT by upregulating the observed E-cadherin expression.
2. Decrease the observed Wnt/β-catenin nuclear translocation through a pathway determined to be dependent on GSK3β. 
3. Inhibited the EMT by downregulating mesenchymal marker proteins like N-cadherin, vimentin, Snail, ZEB-1, and fibronectin; at that same time upregulating epithelial marker proteins like occludin and ZO-1.

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論文出處:Sci Rep. 2019 Mar 26;9(1):5145. doi: 10.1038/s41598-019-41653-9.

論文名稱:Antrodia cinnamomea induces anti-tumor activity by inhibiting the STAT3 signaling pathway in lung cancer cells.

作  者:Huang TT, Lan YW, Chen CM, Ko YF, Ojcius DM, Martel J, Young JD, Chong KY.

出 版 年:2019

分  類:抗癌

論文結論:

Antrodia cinnamomea ethanol extract (ACEE) inhibits lung tumor growth and metastasis by inducing apoptosis and by inhibiting the STAT3 signaling pathway in cancer cells.
1. ACEE treatment increased expression of p53 and Bax, as well as cleavage of caspase-3 and PARP, while reducing expression of survivin and Bcl-2. 
2. ACEE reduced the levels of JAK2 and phosphorylated STAT3 in LLC cells. 
3. In a murine allograft tumor model, oral administration of ACEE significantly inhibited LLC tumor growth and metastasis without affecting serum biological parameters or body weight. ACEE increased cleavage of caspase-3 in murine tumors, while decreasing STAT3 phosphorylation. ACEE reduced the growth of human tumor xenografts in nude mice. 

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論文出處:Carbohydr Polym. 2019 Apr 15;210:175-184. doi: 10.1016/j.carbpol.2019.01.078. Epub 2019 Jan 23.

論文名稱:A sulfated glucan from Antrodia cinnamomea reduces Slug expression through regulation of TGFβ/AKT/GSK3β axis in lung cancer.

作  者:Lin TY, Tseng AJ, Qiu WL, Chao CH, Lu MK.

出 版 年:2019

分  類:抗癌

論文結論:SGA, a sulfated glucan from Antrodia cinnamomea, suppressed tumor growth in vitro and in vivo. TGFβ signaling and overexpression of Slug are regarded as the critical events in lung tumor malignancy. SGA inhibited the TGFβ/FAK/AKT axis by inducing lipid-raft-mediated lysosome-dependent TGFβ receptor degradation, resulting in suppressing cancer cell viability and migration. 

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論文出處:Biomed Pharmacother. 2019 Jan;109:2262-2269. doi: 10.1016/j.biopha.2018.11.101. Epub 2018 Nov 28.

論文名稱:4-Acetylantroquinonol B from antrodia cinnamomea enhances immune function of dendritic cells against liver cancer stem cells.

作  者:Li TY, Chiang BH.

出 版 年:2019

分  類:抗癌

論文結論:

4-acetylantroquinonol B (4-AAQB), a ubiquinone derivative isolated from the mycelium of Antrodia cinnamomea, could inhibit liver cancer stem cell related manifestations and activate the antitumor ability of dendritic cells, and used for liver cancer prevention and immunotherapy.
1. 4-AAQB can inhibit EpCAM, AFP and related pathways of HepG2 cells. Significantly decreases the expression of β-catenin, inhibits the tumorigenicity and decreases the secretion of immune escape related cytokines. 
2. 4-AAQB can stimulate the proliferation of immune cells and promote the endocytosis of immature dendritic cells. 
3. When co-cultured immature dendritic cells with EpCAM+ HepG2 cells, 4-AAQB enhanced the expression of MHC class I and II on the surface of liver cancer stem cells and dendritic cells, increased the expression of costimulatory molecules CD80 of dendritic cells and cytokines related to immune activation. 

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論文出處:Chin J Nat Med. 2019 Jan;17(1):33-42. doi: 10.1016/S1875-5364(19)30007-X.

論文名稱:Secondary metabolites of petri-dish cultured Antrodia camphorata and their hepatoprotective activities against alcohol-induced liver injury in mice.

作  者:Wu Y, Tian WJ, Gao S, Liao ZJ, Wang GH, Lo JM, Lin PH, Zeng DQ, Qiu DR, Liu XZ, Zhou M, Lin T, Chen HF.

出 版 年:2019

分  類:抗癌

論文結論:Nineteen triterpenes were isolated from the petri-dish cultured Antrodia camphorata (PDCA), and thirteen of them were the unique anthroic acids in Antrodia camphorata, including the main content antcin K. In mice alcohol-induced liver injury model, triglyceride (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA) had been reduced by the PDCA powder as well as the main content antcin K, which indicated that the PDCA could protect alcoholic liver injury in mice model and antcin K could be the effective component responsible for the hepatoprotective activities of PDCA against alcoholic liver diseases. triterpenes

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