Ajoene exerts potent effects in 3T3-L1 adipocytes by inhibiting adipogenesis and inducing apoptosis (original) (raw)
Related papers
Organo-Sulphur Garlic Compounds Influence Viability of Mammalian Cells: A Review
Scientia Agriculturae Bohemica, 2018
Garlic is still in the centre of interest for its therapeutic effects. Currently, attention is focused on physiological effects of organo-sulphur garlic compounds, as alliin, allicin, diallyl sulfide (DAS), diallyl disulfide (DADS), diallyl trisulfide (DATS), and S-allyl cysteine (SAC), particularly on their antioxidant and anticancerogenic effects. SAC has been studied for its ability to decrease the production of reactive oxygen species by modulation of the cell glutathione level together with antioxidative enzyme activity, and by improvement of mitochondrial functions. The main mechanism of DAS, DADS, and DATS is the induction of the internal apoptotic pathway. Garlic compounds have the ability to interfere with the signalling pathways of small gaseous signalling molecules known as gasotransmitters – nitric oxide, hydrogen sulfide, and carbon monoxide. The review presents the effect of garlic compounds on cellular oxidative stress, intrinsic apoptotic and gasotransmitter pathways...
Molecular pharmacology, 1998
The pharmacological role of garlic in prevention and treatment of cancer has received increasing attention, but thorough investigations into the molecular mechanisms of action of garlic compounds are rare. The present study demonstrates that ajoene, a major compound of garlic induces apoptosis in human leukemic cells, but not in peripheral mononuclear blood cells of healthy donors. The effect was dose and time dependent. Apoptosis was judged by three criteria, morphology of cells, quantification of subdiploid DNA content by flow cytometry, and detection of DNA fragmentation by gel electrophoresis. Ajoene increased the production of intracellular peroxide in a dose- and time-dependent fashion, which could be partially blocked by preincubation of the human leukemic cells with the antioxidant N-acetylcysteine. Interestingly, N-acetylcysteine-treated cells showed a 50% loss of ajoene-induced apoptosis. Moreover, ajoene was demonstrated to activate nuclear translocation of the transcript...
Molecular Pharmacology, 1998
The pharmacological role of garlic in prevention and treatment of cancer has received increasing attention, but thorough investigations into the molecular mechanisms of action of garlic compounds are rare. The present study demonstrates that ajoene, a major compound of garlic induces apoptosis in human leukemic cells, but not in peripheral mononuclear blood cells of healthy donors. The effect was dose and time dependent. Apoptosis was judged by three criteria, morphology of cells, quantification of subdiploid DNA content by flow cytometry, and detection of DNA fragmentation by gel electrophoresis. Ajoene increased the production of intracellular peroxide in a dose-and time-dependent fashion, which could be partially
Archives of Dermatological Research, 2003
Although the therapeutic role of ajoene, an organosulfur compound of garlic, in cardiovascular diseases and mycology has been established, its usefulness in cancer treatment has only recently been suggested. We applied ajoene topically to the tumors of 21 patients with either nodular or superficial basal cell carcinoma (BCC). A reduction in tumor size was seen in 17 patients. Immunohistochemical assays for Bcl-2 expression in a selection of these tumors before and after treatment showed a significant decrease in this apoptosis-suppressing protein. On average, the percentage of tumor cells expressing the proliferation marker Ki-67 was not decreased, which suggests that the action of ajoene is not explained by a cytostatic effect. To obtain further insight into the mode of action of ajoene, the BCC cell line TE354T and a short-term primary culture of BCC were analyzed for apoptosis induction after treatment with the drug. Apoptosis was detected by morphology of the cells and by flow cytometry. Ajoene induced apoptosis in a dose-and time-dependent manner in these cultures. Taking together the results of the in vivo and in vitro studies, we conclude that ajoene can reduce BCC tumor size, mainly by inducing the mitochondria-dependent route of apoptosis.
Biological properties of garlic and garlic-derived organosulfur compounds
Environmental and Molecular Mutagenesis, 2009
Medicinal properties of garlic (Allium sativum) have been widely known and used since ancient times till the present. Garlic enhances immune functions and has antibacterial, antifungal and antivirus activities. It is known to prevent platelet aggregation, and to have hypotensive and cholesterol-and triglyceride-lowering properties, although the latter features have been questioned. This review is focused on anticancer efficacy of Allium sativum, and attempts to explain the mechanisms of this action. Medicinal properties of garlic rely upon organosulfur compounds mostly derived from alliin. Organosulfur compounds originating from garlic inhibit carcinogen activation, boost phase 2 detoxifying processes, cause cell cycle arrest mostly in G2/M phase, stimulate the mitochondrial apoptotic pathway, increase acetylation of histones. Garlic-derived sulfur compounds influence also gap-junctional intercellular communication and participate in the development of multidrug resistance. This review presents also other little known aspects of molecular action of garlicderived compounds, like modulation of cellular redox state, involvement in signal transduction and post-translational modification of proteins by sulfane sulfur or by formation of mixed disulfides (S-thiolation reactions). Environ. Mol. Mutagen. 50:247-265, 2009. V V C 2009 Wiley-Liss, Inc.
Cell Biochemistry and Function, 2012
The aim of the present studies was to determine whether the mechanism of biological action of garlic-derived sulfur compounds in human hepatoma (HepG2) cells can be dependent on the presence of labile sulfane sulfur in their molecules. We investigated the effect of allyl sulfides from garlic: monosulfide, disulfide and trisulfide on cell proliferation and viability, caspase 3 activity and hydrogen peroxide (H 2 O 2 ) production in HepG2 cells. In parallel, we also examined the influence of the previously mentioned compounds on the levels of thiols, glutathione, cysteine and cysteinyl-glycine, and on the level of sulfane sulfur and the activity of its metabolic enzymes: rhodanese, 3-mercaptopyruvate sulfurtransferase and cystathionase. Among the compounds under study, diallyl trisulfide (DATS), a sulfane sulfur-containing compound, showed the highest biological activity in HepG2 cells. This compound increased the H 2 O 2 formation, lowered the thiol level and produced the strongest inhibition of cell proliferation and the greatest induction of caspase 3 activity in HepG2 cells. DATS did not affect the activity of sulfurtransferases and lowered sulfane sulfur level in HepG2 cells. It appears that sulfane sulfur containing DATS can be bioreduced in cancer cells to hydroperthiol that leads to H 2 O 2 generation, thereby influencing transmission of signals regulating cell proliferation and apoptosis. hydroperthiols with H 2 O 2 generation (Scheme 3). Sulfane sulfur from thiosulfoxide, which is a DADS isomer, does not show such properties. It indicates that only sulfane sulfur released from DATS in the form of hydroperthiol can produce biological activity in HepG2 cells restoring redox regulation, and this is not accompanied by formation of hydropersulfides of proteins.
Diallyl trisulfide suppresses the adipogenesis of 3T3-L1 preadipocytes through ERK activation
Food and Chemical Toxicology, 2012
Garlic and its organosulfur compounds display hypolipidemic effects by inhibiting fatty acid and cholesterol synthesis. We investigated the anti-adipogenic effect of diallyl trisulfide (DATS), the second most abundant organosulfide in garlic oil. We studied the effects of DATS in 3T3-L1 preadipocytes and the mechanism involved in its action. DATS (0-75 lM) inhibited CCAAT/enhancer-binding protein (C/EBP) a and b and peroxisome proliferator-activated receptor (PPAR) c mRNA and protein levels in a doseand time-dependent manner, leading to a decrease of fatty acid synthase (FAS) expression and lipid accumulation in 3T3-L1 cells. Insulin treatment induced a transient increase in ERK phosphorylation in 3T3-L1 preadipocytes, and maximal induction was observed at 5 min and then declined. DATS, however, sustained ERK phosphorylation up to 120 min. In the presence of PD98059, the phosphorylation of ERK and suppression of PPARc expression and DNA binding activity of PPARc by DATS were reversed, and lipid accumulation was restored. In conclusion, these results indicate that DATS inhibits the differentiation of 3T3-L1 preadipocytes into adipocytes. DATS is likely to act by prolonging ERK activation, which leads to the down-regulation of adipogenic transcription factor expression during adipogenesis. Our results suggest that garlic may have potential as an anti-obesity agent.
Journal of Cellular Physiology, 1994
Ajoene (4,5,9-trithiadodeca-1,6,11 -triene-g-oxide), a garlic-derived natural compound, which had been shown to have cytostatickytotoxic properties, was tested with a B cell lymphoma-derived cell line (BJA-B cells) in order to elucidate its mechanism of cytotoxic action. Viability of the cells was determined by the Trypan blue exclusion test and the colorimetric tetrazolium (MTT) assay, whereas metabolic disturbance was evaluated by measuring the pools of reduced (GSH),
1,2-Vinyldithiin from Garlic Inhibits Differentiation and Inflammation of Human Preadipocytes
Journal of Nutrition, 2009
Obesity is a state of chronic low-grade inflammation. Limiting white adipose tissue (WAT) expansion and therefore reducing inflammation could be effective in preventing the progression of obesity and the development of associated complications. We investigated the effects of 1,2-vinyldithiin (1,2-DT), a garlic-derived organosulfur, on the differentiation and inflammatory state of human preadipocytes. Preadipocytes were prepared from subcutaneous adipose tissue of nonobese young women and differentiated in the presence of 1,2-DT. Inflammatory preadipocytes were obtained following treatment with human macrophage-secreted factors. 1,2-DT (100 mmol/L) significantly reduced gene expression of PPARg2 (240%), CCAAT/enhancer binding protein-a (225%), lipoprotein lipase (222%), leptin (230%), and adiponectin (215%). Lipid accumulation was also significantly diminished in preadipocytes differentiated in the presence of 100 mmol/L 1,2-DT (237%) compared with controls. Furthermore, 100 mmol/L 1,2-DT treatment for 10 d significantly reduced PPARg activity (227%). The protein expression of perilipin and the secretion levels for 2 adipokines, leptin and adiponectin, were significantly diminished in 1,2-DT-cultured preadipocytes (237, 251, and 243%, respectively). Moreover, the secretion of inflammatory molecules (interleukin-6 and monocyte chemoattractant protein-1) induced by macrophagesecreted factors was partially abolished in 100 mmol/L 1,2-DT-treated preadipocytes (228 and 225%, respectively). In conclusion, we demonstrated that 1,2-DT, a garlic-derived organosulfur, has antiadipogenic and antiinflammatory actions on human preadipocytes and may be a novel, antiobesity nutraceutical.
Effect of Garlic Oil on Some Biochemical Parameters in Rats Exposed to Hydrogen Peroxide
The Journal of The University of Duhok, 2019
Introduction: Medicinal plants have therapeutic impacts in both modern and traditional medicines. Therefore, some biochemical parameters were investigated in rats fed with garlic oil daily for three weeks. Methods: A total of 20 healthy adult Wister albino male rats aged eight weeks and older were allocated into four equal groups as follow. Group I or control treated with normal diet and water. Group II/ administrated by 1% hydrogen peroxide (H2O2) with drinking water in a dark bottle prepared daily with normal diet. Group III administrated with 5 ml garlic oil added to 25 grams of their ratio for each rat (25oil/125g) also prepared daily with normal drinking water. Group IV also administrated with 5 ml of garlic oil added to 25 gram of their ratio with drinking water that contained1% hydrogen peroxide in a dark bottle. Results: The subjects in the garlic group had significantly lower total cholesterol (54.30 vs. 68.90 mg/dl); VLDL (12.64 vs. 14.62 mg/dl); LDL (32.27 vs. 46.75 mg/dl); and higher HDL (9.39 vs. 7.53 mg/dl)) compared to the control group. The difference in liver and kidney parameters between the control and H2O2 + garlic was not significant. Similarly, no significant difference was found between the garlic and control group in GPT (20.23 vs. 23.38); urea (40.80 vs. 37.10); uric acid (0.53 vs. 0.59); and creatinine (0.57 vs. 0.78); except for GOT (15.80 vs. 30.04). Conclusions: The present study showed the garlic extract is effective to reduce total cholesterol, LDL, VLDL, GOT and increase HDL levels.