• Journal of Plant Biotechnology
• /
• v.48 no.2
• /
• pp.106-114
• /
• 2021

We evaluated the anti-cancer activity against human prostate cancer cells and the associated molecular mechanism of extracts from the branches of Rhamnus yoshinoi (RYB). Treatment with RYB suppressed viability of human prostate cancer cells (PC-3) and decreased protein levels of both β-catenin and T-cell factor 4 (TCF4). This was reflected in reduced TCF4 mRNA, but not decreased β-catenin mRNA. PC-3 cells were pretreated with the proteosome inhibitor MG132 before treatment with RYB, which blocked RYB-mediated down regulation of β-catenin in PC-3 cells, thus confirming that RYB promotes the proteasomal degradation of β-catenin. RYB induced β-catenin phosphorylation, and GSK-3β inhibition by LiCl blocked the phosphorylation and proteasomal degradation of β-catenin by RYB. These results suggest that GSK-3β may be an important upstream kinase for RYB-mediated regulation of β-catenin. Finally, GC/MS analysis of RYB identified 18 compounds. Based on these findings, RYB shows potential for development as a therapeutic agent for prostate cancer.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.4
• /
• pp.2201-2205
• /
• 2013

Colorectal cancer (CRC) is one of the most common cancers in many parts of the world. Its development is a multi-step process involving three distinct stages, initiation that alters the molecular message of a normal cell, followed by promotion and progression that ultimately generates a phenotypically altered transformed malignant cell. Reports have suggested an association of the phosphoinositide-3-kinase (PI3K)/Akt pathway with colon tumorigenesis. Activation of Akt signaling and impaired expression of phosphatase and tensin homolog (PTEN) (a negative regulator of Akt) has been reported in 60-70% of human colon cancers and inhibitors of PI3K/Akt signaling have been suggested as potential therapeutic agents. Around 80% of human colon tumors possess mutations in the APC gene and half of the remainder feature ${\beta}$-catenin gene mutations which affect downstream signaling of the PI3K/Akt pathway. In recent years, there has been a great focus in targeting these signaling pathways, with natural and synthetic drugs reducing the tumor burden in different experiment models. In this review we survey the role of PI3K/Akt/mTOR and Wnt signaling in CRC.

• Journal of Ginseng Research
• /
• v.42 no.2
• /
• pp.133-143
• /
• 2018

Background: AD-2 (20(R)-dammarane-3b, 12b, 20, 25-tetrol; 25-OH-PPD) is a ginsenoside and isolated from Panax ginseng, showing anticancer activity against extensive human cancer cell lines. In this study, effects and mechanisms of 1C ((20R)-3b-O-(L-alanyl)-dammarane-12b, 20, 25-triol), a modified version of AD-2, were evaluated for its development as a novel anticancer drug. Methods: MTT assay was performed to evaluate cell cytotoxic activity. Cell cycle and levels of reactive oxygen species (ROS) were determined using flow cytometry analysis. Western blotting was employed to analyze signaling pathways. Results: 1C concentration-dependently reduces prostate cancer cell viability without affecting normal human gastric epithelial cell line-1 viability. In LNCaP prostate cancer cells, 1C triggered apoptosis via Bcl-2 family-mediated mitochondria pathway, downregulated expression of mouse double minute 2, upregulated expression of p53 and stimulated ROS production. ROS scavenger, N-acetylcysteine, can attenuate 1C-induced apoptosis. 1C also inhibited the proliferation of LNCaP cells through inhibition on $Wnt/{\beta}-catenin$ signaling pathway. Conclusion: 1C shows obvious anticancer activity based on inducing cell apoptosis by Bcl-2 family-mediated mitochondria pathway and ROS production, inhibiting $Wnt/{\beta}-catenin$ signaling pathway. These findings demonstrate that 1C may provide leads as a potential agent for cancer therapy.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.2
• /
• pp.677-681
• /
• 2012

The aim of the present research was to investigate clinicopathologic correlations of immunohistochemically-demonstrated axin (axis inhibition) and ${\beta}$-catenin expression in primary hepatocellular carcinomas (HCCs), in comparison with paraneoplastic, cirrhotic and normal liver tissues. Variation in Axin expression across groups were significant (P < 0.01), correlating with alpha fetoprotein (AFP), HBsAg, cancer plugs in the portal vein, and clinical stage of HCCs(P < 0.05); however, there were no links with sex, age, and tumour size (P > 0.05). Differences in cell membrane ${\beta}$-catenin expression were also statistically significant (P < 0.01), again correlated with AFP, HBsAg, cancer plugs in the portal vein, and clinical stage in HCCs (P < 0.05) but not with sex, age, and tumour size (P > 0.05). Axin expression levels in tissues with reduced membrane ${\beta}$-catenin were low (P < 0.05), also being low with nuclear ${\beta}$-catenin expression (P < 0.05). Axin and ${\beta}$-catenin may play an important role in the genesis and progression of HCC via the Wnt signal transmission pathway. Simultaneous determination of axin, ${\beta}$-catenin, AFP, and HBsAg may be useful for early diagnosis, and metastatic and clinical staging of HCCs.

• Journal of Ginseng Research
• /
• v.42 no.2
• /
• pp.199-207
• /
• 2018

Background: Ginseng is a well-known traditional Chinese medicine that has been widely used in a range of therapeutic and healthcare applications in East Asian countries. Microbial transformation is regarded as an effective and useful technology in modification of nature products for finding new chemical derivatives with potent bioactivities. In this study, three minor derivatives of ginsenoside compound K were isolated and the inducing effects in the Wingless-type MMTV integration site (Wnt) signaling pathway were also investigated. Methods: New compounds were purified from scale-up fermentation of ginsenoside Rb1 by Paecilomyces bainier sp. 229 through repeated silica gel column chromatography and high pressure liquid chromatography. Their structures were determined based on spectral data and X-ray diffraction. The inductive activities of these compounds on the Wnt signaling pathway were conducted on MC3T3-E1 cells by quantitative real-time polymerase chain reaction analysis. Results: The structures of a known 3-keto derivative and two new dehydrogenated metabolites were elucidated. The crystal structure of the 3-keto derivative was reported for the first time and its conformation was compared with that of ginsenoside compound K. The inductive effects of these compounds on osteogenic differentiation by activating the Wnt/b-catenin signaling pathway were explained for the first time. Conclusion: This study may provide a new insight into the metabolic pathway of ginsenoside by microbial transformation. In addition, the results might provide a reasonable explanation for the activity of ginseng in treating osteoporosis and supply good monomer ginsenoside resources for nutraceutical or pharmaceutical development.

• Korean Journal of Pharmacognosy
• /
• v.52 no.1
• /
• pp.34-40
• /
• 2021

Proliferation and maintain of dermal papilla during progression of hair-cycle are crucial to the duration of anagen and regulated by diverse signaling pathway such as PI3K/Akt/Wnt/β-catenin pathway. In this study, we investigated the effects and mechanisms of Viola verecunda on dermal papilla cells. Treatment of dermal papilla cells with whole plant extract of V. verecunda resulted in cell proliferation, which was accompanied by up-regulation of cyclin D1, phospho (ser780)-pRB and cdc2 p34, and down-regulation of p27kip1. V. verecunda extract also promoted the levels of phospho (ser473)-Akt and phospho (ser780)-pRB in a time-dependent manner. Inhibition of PI3K/Akt by Wortmannin suppressed progression of cell-cycle, thereby attenuated the increases in proliferation of dermal papilla cells by V. verecunda extract. We further investigated Wnt/β-catenin pathway with respect to the effects of V. verecunda extract on the proliferation of dermal papilla cells. Treatment with V. verecunda extract results in up-regulation of Wnt/β-catenin proteins such as phospho (ser9)-GSKβ, phospho (ser552)-β-catenin and phospho (ser675)-β-catenin. In addition, Wortmannin abrogated V. verecunda extract mediated up-regulation of cdc2 p34 and down-regulation of p27kip1. These finding reveal that the proliferative effect of V. verecunda mediated by alteration of cell-cycle via activating PI3K/Akt/Wnt pathway in dermal papilla cells.

• Animal Bioscience
• /
• v.37 no.3
• /
• pp.471-480
• /
• 2024

Objective: The objective of this study was to investigate the regulation relationship of Ten-eleven translocation 1 (Tet1) in DNA demethylation and the proliferation of primordial germ cells (PGCs) in chickens. Methods: siRNA targeting Tet1 was used to transiently knockdown the expression of Tet1 in chicken PGCs, and the genomic DNA methylation status was measured. The proliferation of chicken PGCs was detected by flow cytometry analysis and cell counting kit-8 assay when activation or inhibition of Wnt4/β-catenin signaling pathway. And the level of DNA methylation and hisotne methylation was also tested. Results: Results revealed that knockdown of Tet1 inhibited the proliferation of chicken PGCs and downregulated the mRNA expression of Cyclin D1 and cyclin-dependent kinase 6 (CDK6), as well as pluripotency-associated genes (Nanog, PouV, and Sox2). Flow cytometry analysis confirmed that the population of PGCs in Tet1 knockdown group displayed a significant decrease in the proportion of S and G2 phase cells, which meant that there were less PGCs entered the mitosis process than that of control. Furthermore, Tet1 knockdown delayed the entrance to G1/S phase and this inhibition was rescued by treated with BIO. Consistent with these findings, Wnt/β-catenin signaling was inactivated in Tet1 knockdown PGCs, leading to aberrant proliferation. Further analysis showed that the methylation of the whole genome increased significantly after Tet1 downregulation, while hydroxyl-methylation obviously declined. Meanwhile, the level of H3K27me3 was upregulated and H3K9me2 was downregulated in Tet1 knockdown PGCs, which was achieved by regulating Wnt/β-catenin signaling pathway. Conclusion: These results suggested that the self-renewal of chicken PGCs and the maintenance of their characteristics were regulated by Tet1 mediating DNA demethylation through the activation of Wnt4/β-catenin signaling pathway.

• Molecules and Cells
• /
• v.43 no.9
• /
• pp.774-783
• /
• 2020

The lung has a vital function in gas exchange between the blood and the external atmosphere. It also has a critical role in the immune defense against external pathogens and environmental factors. While the lung is classified as a relatively quiescent organ with little homeostatic turnover, it shows robust regenerative capacity in response to injury, mediated by the resident stem/progenitor cells. During regeneration, regionally distinct epithelial cell populations with specific functions are generated from several different types of stem/progenitor cells localized within four histologically distinguished regions: trachea, bronchi, bronchioles, and alveoli. WNT signaling is one of the key signaling pathways involved in regulating many types of stem/progenitor cells in various organs. In addition to its developmental role in the embryonic and fetal lung, WNT signaling is critical for lung homeostasis and regeneration. In this minireview, we summarize and discuss recent advances in the understanding of the role of WNT signaling in lung regeneration with an emphasis on stem/progenitor cells.

• Journal of the Korean Applied Science and Technology
• /
• v.37 no.4
• /
• pp.674-681
• /
• 2020

The root of Codonopsis lanceolata has been used in traditional medicine. This study was conducted to confirm the comparative effect of ethanol solvent extraction (CLE) and supercritical carbon dioxide extraction (CLS) of C. lanceolata roots. CLS had higher antioxidant than CLE. For supercritical co-solvent modified carbon dioxide extraction (CLS), it were extracted at 250 bar 50℃ 150 min at a flow rate of ethyl alcohol 3 mL/min for 90min. In addition, CLS inhibited the adipocyte differentiation of 3T3-L1 cells. When treated with the extract at a concentration of 100 ㎍/mL, the Wnt/β-catenin pathway reporter luciferase activity of HEK 293-TOP cells increased approximately by 3-folds compared to that of the untreated control group. Also, the treatment by CLS (50 ㎍/mL) showed a significant increase of involucrin expression. These results indicate that supercritical carbon dioxide extract of C. lanceolatamay serve as a cosmeceutical agent for improving skin barrier function and the treatment of obesity.

• Journal of Microbiology and Biotechnology
• /
• v.31 no.11
• /
• pp.1559-1567
• /
• 2021

The root bark of Morus alba L. has cytotoxic activity against several types of cancer cells. However, little is known about its chemopreventive mechanisms and bioactive metabolites. In this study, we showed that M. alba L. root bark extracts (MRBE) suppressed β-catenin response transcription (CRT), which is aberrantly activated in various cancers, by promoting the degradation of β-catenin. In addition, MRBE repressed the expression of the β-catenin/T-cell factor (TCF)-dependent genes, c-myc and cyclin D1, thus inhibiting the proliferation of RPMI-8226 multiple myeloma (MM) cells. MRBE induced apoptosis in MM cells, as evidenced by the increase in the population of annexin VFITC-positive cells and caspase-3/7 activity. We identified ursolic acid in MRBE through LC/mass spectrum (MS) and observed that it also decreased intracellular β-catenin, c-myc, and cyclin D1 levels. Furthermore, it suppressed the proliferation of RPMI-8226 cells by stimulating cell cycle arrest and apoptosis. These findings suggest that MRBE and its active ingredient, ursolic acid, exert antiproliferative activity by promoting the degradation of β-catenin and may have significant chemopreventive potential against MM.