• Animal Bioscience
• /
• v.35 no.5
• /
• pp.763-777
• /
• 2022

Objective: Excessive lipid accumulation in adipocytes results in prevalence of obesity and metabolic syndrome. Curcumin (CUR), a naturally phenolic active ingredient, has been shown to have lipid-lowering effects. However, its underlying mechanisms have remained largely unknown. Therefore, the study aims to determine the effect of CUR on cellular lipid accumulation in porcine subcutaneous preadipocytes (PSPA) and to clarify novel mechanisms. Methods: The PSPA were cultured and treated with or without CUR. Both cell counting Kit-8 and lactate dehydrogenase release assays were used to examine cytotoxicity. Intracellular lipid contents were measured by oil-red-o staining extraction and triglyceride quantification. Apoptosis was determined by flow cytometry and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-nick end labelling assay. Adipogenic and apoptosis genes were analyzed by quantitative polymerase chain reaction and Western blot. Results: The CUR dose-dependently reduced the proliferation and lipid accumulation of PSPA. Noncytotoxic doses of CUR (10 to 20 μM) significantly inhibited extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and expression of adipogenic genes peroxisome proliferation-activity receptor-γ (PPAR-γ), CCAAT/enhancer binding protein-α, sterol regulatory element-binding protein-1c, adipocyte protein-2, glucose transporter-4 as well as key lipogenic enzymes fatty acid synthase and acetyl-CoA carboxylase, while ERK1/2 activation significantly reversed CUR-reduced lipid accumulation by increasing PPAR-γ. Furthermore, compared with differentiation induced media treated cells, higher dose of CUR (30 μM) significantly decreased the expression of AKT and B-cell lymphoma-2 (BCL-2), while increased the expression of BCL-2-associated X (BAX) and the BAX/BCL-2 expression ratio, suggesting triggered apoptosis by inactivating AKT and increasing BAX/BCL-2 ratio and Caspase-3 expression. Moreover, AKT activation significantly rescued CUR inhibiting lipid accumulation via repressing apoptosis. Conclusion: These results demonstrate that CUR is capable of suppressing differentiation by inhibiting ERK1/2-PPAR-γ signaling pathway and triggering apoptosis via decreasing AKT and subsequently increasing BAX/BCL-2 ratio and Caspase-3, suggesting that CUR provides an important method for the reduction of porcine body fat, as well as the prevention and treatment of human obesity.

• Journal of Life Science
• /
• v.33 no.4
• /
• pp.349-356
• /
• 2023

Gout, a chronic inflammatory arthritic disease, is characterized by hyperuricemia. Gout can be induced by an inflammatory response to monosodium urate (MSU) crystals mediated by pro-inflammatory cytokine release following activation of the NOD-like receptor protein 3 (NLRP3) inflammasome. Many sulfur-containing phytochemical compounds in garlic (Allium sativum L.) are considered active ingredients because of their potential pharmacological benefits for various diseases, but their efficacy in NLRP3 inflammasome activation-mediated gout has not been demonstrated. In this study, we investigated whether diallyl disulfide (DADS) and diallyl trisulfide (DATS), representative garlic-derived sulfur compounds, have an inhibitory effect on MSU-induced NLRP3 inflammasome activation. Our results showed that under non-cytotoxic conditions, DADS and DATS significantly blocked nitric oxide production and interleukin (IL)-1β release in response to MSU in lipopolysaccharide (LPS)-primed RAW 264.7 macrophages. DADS and DATS also attenuated enhanced expression of NLRP3 and its adapter protein, apoptosis-associated speck-like protein, which was associated with downregulation of and caspase-1 p20 and IL-1β expression, suggesting that MSU-induced LRP3 inflammasome activation was counteracted by DADS and DATS. Furthermore, DADS and DATS blocked oxidative stress, an upstream event for NLRP3 inflammasome activation, as evidenced by the fact that they scavenged reactive oxygen species (ROS) production. Taken together, our findings demonstrate that DADS and DATS suppressed NLRP3 inflammasome activation by inhibiting the ROS/NLRP3 pathway and that they have potential as treatments for NLRP3-dependent gouty arthritis.

• Biomedical Science Letters
• /
• v.15 no.2
• /
• pp.147-152
• /
• 2009

Lycopus lucid us Turcz is well known as traditional Chinese medicine, and it has been shown to exhibit antiinflammatory, -allergic and -oxidative effect. However, its anti-cancer properties have not been examined yet. In this study, we investigated the effect of the methanol extract of Lycopus lucid us Turcz on anti-cancer effect in MCF-7 human breast cancer cells. Treatment of Lycopus lucidus Turcz extract induced apoptosis and inhibition of cell proliferation in dose- and time-dependent manner. Apoptosis in the MCF-7 cells was characterized with the changes in nuclear morphology; decrease of Bcl-2 and caspase-7 expression; and increase of cleaved poly ADP-ribose polymerase(PARP). Furthermore, treatment of Lycopus lucidus Turcz extract caused the down-regulation of cell cycle-related protein including, cdk4, cyclin D1 and E2F-1. These results suggest that Lycopus lucidus Turcz might have the therapeutic value against human breast cancer cells.

• Biomolecules & Therapeutics
• /
• v.11 no.2
• /
• pp.112-118
• /
• 2003

1-Methylated $\beta$-carbolines (harmaline and harmalol) and antioxidants (N-acetylcysteine and ascorbate) reduced the loss of cell viability in differentiated PC 12 cells treated with 5 mM glutamate. $\beta$-Carbolines prevented the glutamate-induced decrease in mitochondrial membrane potential, cytochrome c release and caspase-3 activation in PC 12 cells. $\beta$-Carbolines reduced the formation of reactive oxygen species and depletion of glutathione due to glutamate in PC12 cells. $\beta$-Carbolines revealed a scavenging action on hydrogen peroxide and reduced the iron and EDTA-mediated degradation of 2-deoxy-D-ribose. The results suggest that I-methylated $\beta$-carbolines attenuate the cytotoxic effect of glutamate on PC12 cells by reducing the alteration of mitochondrial membrane permeability that seems to be mediated by oxidative stress.

• The Korean Journal of Physiology and Pharmacology
• /
• v.10 no.4
• /
• pp.207-212
• /
• 2006

Mitochondrial permeability transition has been shown to be involved in neuronal cell death. Mitochondrial monoamine oxidase (MAO)-B is considered to play a part in the progress of nigrostriatal cell death. The present study examined the effect of MAO inhibitors against the toxicity of 1-methyl-4-phenylpyridinium $(MPP^+)$ in relation to the mitochondrial permeability transition. Chlorgyline (a selective inhibitor of MAO-A), deprenyl (a selective inhibitor of MAO-B) and tranylcypromine (nonselective inhibitor of MAO) all prevented cell viability loss, cytochrome c release, caspase-3 activation, formation of reactive oxygen species and depletion of GSH in differentiated PC12 cells treated with $500\;{\mu}M$$MPP^+$. The MAO inhibitors at $10\;{\mu}M$ revealed a maximal inhibitory effect and beyond this concentration the inhibitory effect declined. On the basis of concentration, the inhibitory potency was tranylcypromine, deprenyl and chlorgyline order. The results suggest that chlorgyline, deprenyl and tranylcypromine attenuate the toxicity of $MPP^+$ against PC12 cells by suppressing the mitochondrial permeability transition that seems to be mediated by oxidative stress.

• Toxicological Research
• /
• v.21 no.4
• /
• pp.303-307
• /
• 2005

Nanomaterials, which ranges in size from 1 to 100 nm, have been used to create uqnique devices at the nanoscale level possessing novel physical and chemical functional properties. However, the toxicities of nanomaterials have not been fully tested and the risk of nanomaterials is emerging issues in these days. In this study, the cytotoxicity of copper nanoparticles was tested in cultured human bronchial epithelial cells. As a results, copper nanoparticles showed cytotoxicity similar with cupric ion and the apoptotic mechanisms of DNA fragmentation and caspase-3 activation were involved. Induction of heme oxygenase-1 and thioredoxin reductase by copper nanoparticles indicated that cytotoxicity of copper nanoparticles is likely to be mediated through oxidative stress.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 2003.11a
• /
• pp.86-86
• /
• 2003

In a continuous effort to develop novel anticancer agents we newly synthesized and evaluated the antitumor activity of nucleoside analogues. One analogue, 4 - ［2-Chlor-6- (3-iodo- benzy lamino) -purin -9-yl］- 2,3-dihydroxy-cyclopentanecarbo xylic acid methylamide (LJ-331), has been shown to exert a potent inhibition of human cancer cell growth in vitro including human lung (A549), stomach (SNU-638) and leukemia (HL-60) cancer cells. Following mechanism of action study revealed that LJ - 331induces cell cycle arrest at the G1 phase in HL-60 cells and evokes apoptotic phenomena such as an increase in DNA ladder intensity and chromatin condensation by a dose- and time-dependent manner. LJ-331 also activated the caspase-3 activity in HL-60. This result suggests that the growth inhibition of human cancer cells by LJ-331 might be related to the cell cycle arrest and induction of apoptosis.

• BMB Reports
• /
• v.49 no.5
• /
• pp.247-248
• /
• 2016

Necroptosis is a well-known form of caspase-independent cell death. Necroptosis can be triggered by various extrinsic stimuli, including death ligands in the presence of receptorinteracting protein kinase 3 (RIPK3), a key mediator of necroptosis induction. Our recent studies have revealed that C-terminus HSC-70 interacting protein (CHIP), an E3 ligase, can function as an inhibitor of necroptosis. CHIP^−/− mouse embryonic fibroblast showed higher sensitivity to necrotic stimuli than wild-type mouse embryonic fibroblast cells. Deleterious effects of CHIP knockout MEFs were retrieved by RIPK3 depletion. We found that CHIP negatively regulated RIPK3 and RIPK1 by ubiquitylation- and lysosome- dependent degradation. In addition, CHIP^−/− mice showed postnatal lethality with intestinal defects that could be rescued by crossing with RIPK3^−/− mice. These results suggest that CHIP is a negative regulator of RIPK1 and RIPK3, thus inhibiting necroptosis.

• Proceedings of the Korean Society of Life Science Conference
• /
• 2008.10a
• /
• pp.48.1-48.1
• /
• 2008

• Biomolecules & Therapeutics
• /
• v.20 no.1
• /
• pp.62-67
• /
• 2012

TNF-related apoptosis-inducing ligand (TRAIL) is a promising agent for management of cancer because of its selective cytotoxicity to cancer cells. However, some cancer cells have resistance to TRAIL. Accordingly, novel treatment strategies are required to overcome TRAIL resistance. Here, we examined the synergistic apoptotic effect of apigenin in combination with TRAIL in Huh-7 cells. We found that combined treatment of TRAIL and apigenin markedly inhibited Huh-7 cell growth compared to either agent alone by inducing apoptosis. Combined treatment with apigenin and TRAIL induced chromatin condensation and the cleavage of poly (ADP-ribose) polymerase (PARP). In addition, enhanced apoptosis by TRAIL/apigenin combination was quantified by annexin V/PI flow cytometry analysis. Western blot analysis suggested that apigenin sensitizes cells to TRAIL-induced apoptosis by activating both intrinsic and extrinsic apoptotic pathway-related caspases. The augmented apoptotic effect by TRAIL/apigenin combination was accompanied by triggering mitochondria-dependent signaling pathway, as indicated by Bax/Bcl-2 ratio up-regulation. Our results demonstrate that combination of TRAIL and apigenin facilitates apoptosis in Huh-7 cells.