• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.15
• /
• pp.6549-6556
• /
• 2015

The PI3K-Akt-mTOR, $Wnt/{\beta}$-catenin and apoptosis signaling pathways have been shown to be involved in genesis of colorectal cancer (CRC). The aim of this study was to elucidate whether combination of Gelam honey and ginger might have chemopreventive properties in HT29 colon cancer cells by modulating the mTOR, $Wnt/{\beta}$-catenin and apoptosis signaling pathways. Treatment with Gelam honey and ginger reduced the viability of the HT29 cells dose dependently with $IC_{50}$ values of 88 mg/ml and 2.15 mg/ml respectively, their while the combined treatment of 2 mg/ml of ginger with 31 mg/ml of Gelam honey inhibited growth of most HT29 cells. Gelam honey, ginger and combination induced apoptosis in a dose dependent manner with the combined treatment exhibiting the highest apoptosis rate. The combined treatment downregulated the gene expressions of Akt, mTOR, Raptor, Rictor, ${\beta}$-catenin, $Gsk3{\beta}$, Tcf4 and cyclin D1 while cytochrome C and caspase 3 genes were shown to be upregulated. In conclusion, the combination of Gelam honey and ginger may serve as a potential therapy in the treatment of colorectal cancer through inhibiton of mTOR, $Wnt/{\beta}$ catenin signaling pathways and induction of apoptosis pathway.

• Natural Product Sciences
• /
• v.19 no.2
• /
• pp.155-159
• /
• 2013

Honokiol, a naturally occurring neolignan mainly found in Magnolia species, has exhibited a potential anti-proliferative activity in human cancer cells. However, the growth inhibitory activity against hepatocellular carcinoma cells and the underlying molecular mechanisms has been poorly determined. The present study was designed to examine the anti-proliferative effect of honokiol in SK-HEP-1 human hepatocellular cancer cells. Honokiol exerted anti-proliferative activity with cell-cycle arrest at the G0/G1 phase and sequential induction of apoptotic cell death. The cell-cycle arrest was well correlated with the down-regulation of checkpoint proteins including cyclin D1, cyclin A, cyclin E, CDK4, PCNA, retinoblastoma protein (Rb), and c-Myc. The increase of sub-G1 peak by the higher concentration of honokiol ($75{\mu}M$) was closely related to the induction of apoptosis, which was evidenced by decreased expression of Bcl-2, Bid, and caspase-9. Hohokiol was also found to attenuate the activation of signaling proteins in the Akt/mTOR and ERK pathways. These findings suggest that the anti-proliferative effect of honokiol was associated in part with the induction of cell-cycle arrest, apoptosis, and dow-nregulation of Akt/mTOR signaling pathways in human hepatocellular cancer cells.

• BMB Reports
• /
• v.57 no.2
• /
• pp.92-97
• /
• 2024

Elevated blood glucose is associated with an increased risk of atherosclerosis. Data from the current study showed that glucosamine (GlcN), a normal glucose metabolite of the hexosamine biosynthetic pathway (HBP), promoted lipid accumulation in RAW264.7 macrophage cells. Oleic acid- and lipopolysaccharide (LPS)-induced lipid accumulation was further enhanced by GlcN in RAW264.7 cells, although there was no a significant change in the rate of fatty acid uptake. GlcN increased acetyl CoA carboxylase (ACC), fatty acid synthase (FAS), scavenger receptor class A, liver X receptor, and sterol regulatory element-binding protein-1c (SREBP-1c) mRNA expression, and; conversely, suppressed ATP-binding cassette transporter A1 (ABCA-1) and ABCG-1 expression. Additionally, GlcN promoted O-GlcNAcylation of nuclear SREBP-1 but did not affect its DNA binding activity. GlcN stimulated phosphorylation of mammalian target of rapamycin (mTOR) and S6 kinase. Rapamycin, a mTOR-specific inhibitor, suppressed GlcN-induced lipid accumulation in RAW264.7 cells. The GlcN-mediated increase in ACC and FAS mRNA was suppressed, while the decrease in ABCA-1 and ABCG-1 by GlcN was not significantly altered by rapamycin. Together, our results highlight the importance of the mTOR signaling pathway in GlcN-induced macrophage lipid accumulation and further support a potential link between mTOR and HBP signaling in lipogenesis.

• Computers and Concrete
• /
• v.2 no.6
• /
• pp.455-479
• /
• 2005

This paper describes a 2D nonlinear finite element analysis (NLFEA) platform that combines heat flow analysis with realistic analysis of cracked reinforced concrete structures. The behavior models included in the structural analysis are mainly based on the Modified Compression Field Theory and the Distributed Stress Field Model. The heat flow analysis takes into account time-varying thermal loads and temperature-dependent material properties. The capability of 2D nonlinear transient thermal analysis is then implemented into a nonlinear finite element analysis program VecTor2(C) for 2D reinforced concrete membranes. Analyses of four numerical examples are performed using VecTor2, and results obtained indicate that the suggested nonlinear finite element analysis procedure is capable of modeling the complete response of a concrete structure to thermal and mechanical loads.

• Journal of Animal Science and Technology
• /
• v.54 no.5
• /
• pp.369-373
• /
• 2012

AMP-activated protein kinase (AMPK) maintains energy homeostasis in skeletal muscle. Nonetheless, its functional role on protein synthesis with different nutrient availability has not been elucidated. Therefore, the purpose of this study is to examine the effect of AMPK activity on protein content in C2C12 myotubes incubated with low (5 mM; LG) or high (25 mM; HG) glucose media. LG stimulated (p<0.05) AMPK and acetyl CoA carboxylase (ACC) activity compare to those in HG group. Total protein content was higher in myotubes cultured with HG than in those cultured with LG and further increased by AICAR (5-amino-1-${\beta}$-D-ribofuranosyl-imidazole-4-carboxamide). Myotubes cultured with HG showed 7.5% lower UbFL (Ubiquitin Firefly Luciferase)-to-SV40 (Simian virus40) ratio compared to those in LG. Glucose level did not change the phosphorylation level of mammalian target of rapamycin (mTOR). Interestingly, administration of AICAR significantly increased phosphorylation level of mTOR in myotubes cultured with LG but not in those with HG. Overall, this data indicate that AMPK activity and protein turnover are finely regulated in response to different glucose concentration.

• Journal of Life Science
• /
• v.26 no.6
• /
• pp.663-672
• /
• 2016

The Cnidium monnieri (L.) Cusson is an annual plant distributed in China and Korea. The fruit of C. monnieri is used as a medicinal herb that is effective for the treatment of carbuncle and pain in female genitalia. However, the anti-cancer effects of CME have not yet been reported. In this study, we assessed the apoptotic effects and cell cycle arrest effects of ethanol extracts from C. monnieri on HCT116 colon cancer cells. The results of an MTT assay and LDH assay demonstrated a decrease in cell viability and the cytotoxic effects of CME. In addition, the number of apoptotic body and the apoptotic rate were increased in a dose-dependent manner through Hoechst 33342 staining and Annexin V-PI double staining. In addition, cell cycle arrest occurred at the G1 phase by CME. Protein kinase B (Akt) plays an important role in cancer cell survival, growth, and division. Akt down-regulates apoptosis-mediated proteins, such as mammalian target of rapamycin (mTOR), p53, and Glycogen Synthase kinase-3β (GSK-3β). CME could regulate the expression levels of p-Akt, p-mTOR, p-GSK-3β, Bcl-2 family members, caspase-3, and PARP. Furthermore, treatment with CME, LY294002 (PI3K/Akt inhibitor), BIO (GSK-3β inhibitor), and Rapamycin (mTOR inhibitor) showed that apoptotic effects occurred through the regulation of the AKT/mTOR/GSK-3β signaling pathway. Our results demonstrated CME could induce apoptosis and cell cycle arrest in HCT116 colon cancer cells.

• Journal of Life Science
• /
• v.26 no.4
• /
• pp.387-397
• /
• 2016

The purpose of this study was to determine if heat shock proteins are involved in autophagy in skeletal muscle. We used the autophagy flux strategy, which is an LC3 II/p62 turnover assay conducted with and without an autophagy inhibitor, to determine whether 17-DMAG (an Hsp90 inhibitor/Hsp72 activator) stimulates autophagy in skeletal muscle. We treated C2C12 cells with 17-DMAG (500 nM) for 24 hr with and without the autophagy inhibitor (Bafilomycin A1, 200 ng/ml), and we injected C57BL/6 mice i.p. with 17-DMAG (10 mg/kg) daily for 7 days with and without colchicine as an autophagy inhibitor (0.4 mg/kg/day, administered on the last 2 days). C2C12 myotubes and tibialis anterior muscles were harvested for analysis of mTOR-dependent autophagy signaling pathway proteins and autophagic marker proteins (p62 and LC3 II) by Western blot analysis. The blots showed that 17-DMAG upregulated hsp72 and decreased Akt protein levels and S6 phosphorylation in C2C12 cells. However, an in vitro autophagic flux assay demonstrated that 17-DMAG did not increase LC3 II and p62 protein concentrations to a greater extent than Bafilomycin A1 treatment alone. Similarly, 17-DMAG increased Hsp72 protein levels and decreased the expression of Akt and the phosphorylation of S6 in mouse skeletal muscle. However, unlike the response seen in C2C12 myotubes, the p62 protein levels were significantly decreased in 17-DMAG-treated mouse skeletal muscle (~50%; p<0.05). The LC3 II protein levels in 17-DMAG-treated mice were increased ~2-fold more when degradation was inhibited by colchicine (p<0.01). This suggests that 17-DMAG stimulates basal autophagy in skeletal muscle but is not found in C2C12 myotubes.

• Fisheries and Aquatic Sciences
• /
• v.27 no.5
• /
• pp.283-293
• /
• 2024

Mahseer (Tor soro) growth performance tends to be slow, necessitating further development and intensification of cultivation. One way to develop aquaculture intensification is to manipulate cultivation containers to create optimal environmental conditions for the mahseer to grow. This study aimed to examine the body performance and growth performance of mahseer reared in different colored containers. Experimental research with completely randomized design was employed, with four colored container treatments namely treatment A (transparent), B (green), C (blue), and D (black), with four replications in each treatment. Findings indicate that different rearing media colors had significant effect on absolute length (4.68 ± 0.24 cm), absolute weight (1.58 ± 0.35 g), specific growth rate (2.17 ± 0.38%), feed conversion ratio (2.87 ± 0.04), survival rate (100 ± 0.00%), gross energy (3,816 ± 65.05 cal/g), and body proximate. Physiologically, mahseer fish bred using blue and black containers tend to be more resistant to stress.The best body performance and growth performance were observed in the blue and black colored containers.

• Journal of Ginseng Research
• /
• v.47 no.6
• /
• pp.726-734
• /
• 2023

Background: Skeletal muscles play a key role in physical activity and energy metabolism. The loss of skeletal muscle mass can cause problems related to metabolism and physical activity. Studies are being conducted to prevent such diseases by increasing the mass and regeneration capacity of muscles. Ginsenoside Rg5 has been reported to exhibit a broad range of pharmacological activities. However, studies on the effects of Rg5 on muscle differentiation and growth are scarce. Methods: To investigate the effects of Rg5 on myogenesis, C2C12 myoblasts were induced to differentiate with Rg5, followed by immunoblotting, immunostaining, and qRT-PCR for myogenic markers and promyogenic signaling (p38MAPK). Immunoprecipitation confirmed that Rg5 increased the interaction between MyoD and E2A via p38MAPK. To investigate the effects of Rg5 on prevention of muscle mass loss, C2C12 myotubes were treated with dexamethasone to induce muscle atrophy. Immunoblotting, immunostaining, and qRT-PCR were performed for myogenic markers, Akt/mTOR signaling for protein synthesis, and atrophy-related genes (Atrogin-1 and MuRF1). Results: Rg5 promoted C2C12 myoblast differentiation through phosphorylation of p38MAPK and MyoD/E2A heterodimerization. Furthermore, Rg5 stimulated C2C12 myotube hypertrophy via phosphorylation of Akt/mTOR. Phosphorylation of Akt induces FoxO3a phosphorylation, which reduces the expression of Atrogin-1 and MuRF1. Conclusion: This study provides an understanding of how Rg5 promotes myogenesis and hypertrophy and prevents dexamethasone-induced muscle atrophy. The study is the first, to the best of our knowledge, to show that Rg5 promotes muscle regeneration and to suggest that Rg5 can be used for therapeutic intervention of muscle weakness and atrophy, including cancer cachexia.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.34 no.2
• /
• pp.61-66
• /
• 2020

Epithelial-mesenchymal transition (EMT) is the process by which epithelial cells lose their characters and acquire the properties of mesenchymal cells. EMT has been reported to exert an essential role in embryonic development. Recently, EMT has emerged as a pivotal mechanism in the metastasis of cancer and the fibrosis of chronic diseases. In particular, EMT is drawing attention as a mechanism of renal fibrosis in chronic kidney diseases such as diabetic nephropathy. In this study, we developed an EMT model by treating TGF-β1 on the podocytes, which play a key role in the renal glomerular filtration. This study explored the effects of Hwanggeum-tang (HGT) recorded in Dongeuibogam as being able to be used for the treatment of Sogal whose concept had been applied to Diabetes Mellitus (DM), on the TGF-β1-induced podocyte EMT. HGT suppressed the expression of vimentin and α-SMA, the EMT marker, in the human podocytes stimulated by TGF-β1. However, HGT increased the expression of ZO-1 and nephrin. Interestingly, HGT selectively inhibited the mTOR pathway rather than the classical Smad pathway. HGT also activated the AMPK signaling. HGT's inhibitory effect on the podocyte EMT through regulation of the mTOR pathway was achieved through the activation of AMPK, which was confirmed by comparison with cells treated with compound C (CC), an inhibitor of AMPK signaling. In conclusion, HGT can be applied to the renal fibrosis by preventing TGF-β1-induced EMT of podocytes through AMPK activation and mTOR inhibition.