Ajoene, a Compound of Garlic, Induces Apoptosis in Human Promyeloleukemic Cells, Accompanied by Generation of Reactive Oxygen Species and Activation of Nuclear Factor κB (original) (raw)
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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...
Induction of apoptosis by a hexane extract of aged black garlic in the human leukemic U937 cells
Nutrition research and practice, 2014
In this study, the apoptogenic activity and mechanisms of cell death induced by hexane extract of aged black garlic (HEABG) were investigated in human leukemic U937 cells. Cytotoxicity was evaluated by MTT (3-(4, 5-dimethyl-thiazol-2-yl)-2, 5-diphenyl tetrazoliumbromide) assay. Apoptosis was detected using 4,6-diamidino-2-phenyllindile (DAPI) staining, agarose gel electrophoresis and flow cytometry. The protein levels were determined by Western blot analysis. Caspase activity was measured using a colorimetric assay. Exposure to HEABG was found to result in a concentration- and time-dependent growth inhibition by induction of apoptosis, which was associated with an up-regulation of death receptor 4 and Fas legend, and an increase in the ratio of Bax/Bcl-2 protein expression. Apoptosis-inducing concentrations of HEABG induced the activation of caspase-9, an initiator caspase of the mitochodrial mediated intrinsic pathway, and caspase-3, accompanied by proteolytic degradation of poly(A...
Journal of cancer science & therapy, 2012
Garlic supplementation in diet has been shown to be beneficial to cancer patients. Recently, its pharmacological role in the prevention and treatment of cancer has received increasing attention. However, the mechanisms by which garlic extract (GE) induces cytotoxicity, oxidative stress, and apoptosis in cancer cells remain largely unknown. The present study was designed to use HL-60 cells as a test model to evaluate whether or not GE-induced cytotoxicty and apoptosis in human leukemia (HL-60) cells is mediated through oxidative stress. Human leukemia (HL-60) cells were treated with different concentrations of GE for 12 hr. Cell survival was determined by MTT assay. The extent of oxidative cell/tissue damage was determined by measuring malondialdehyde (lipid peroxidation biomarker) concentrations by spectrophotometry. Cell apoptosis was measured by flow cytometry assessment (Annexin-V and caspase-3 assays) and agarose gel electrophoresis (DNA laddering assay). Data obtained from the ...
Garlic Induced Apoptosis, Cell Cycle Check Points and Inhibition of Cancer Cell Proliferation
Present review article describing effects of garlic components on induction of apoptosis, cell cycle check points and inhibition of cancer cell proliferation. Garlic derived organic compounds hold unique therapeutic potential and induces apoptotic signaling pathways; do cell cycle arrest, and show cytotoxic and anti-invasive activity to a variety of cancer cells. Regular dietary intake of garlic cut down neoplastic growth, cancer cell proliferation, and induces programmed cell death. Garlic components act as tumor suppressor agents and prevent aberrant cell expansion by slowing down the cell cycle, or by inducing apoptosis. These apoptosis inducers can act on various apoptosis-related proteins to promote apoptotic cell death. Garlic based nanoformulations can target oncogenic mutations which disrupt apoptosis. These can inhibit cellular changes leading to tumor initiation, progression of metastasis. Garlic derivatives can control DNA damage thereby slow down oncogenic changes and induce caspase activity which halts or stalls mutation in p53 gene and thereby stops growth of lung, colon, and breast cancer. More often, new combinations of garlic components may stop cancer progression as well as multistage carcinogenesis. No doubt garlic components can be used in designing best possible molecular targets of cancer cells and that could be recommended for clinical management of different types of cancer.
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.
Journal of Applied Pharmaceutical Science, 2018
Background: Garlic (Allium sativum) with its main component organosulfur compounds (OSCs) has an anticancer effect against a large verity of cancer cells. This anticancer effect was studied on individual garlic components, rather than fractions. Methods: Herein, we investigated the anticancer effect of different garlic fractions on the MCF7 and HepG2 cells and studied the underlying mechanism. Results: Different garlic fractions, extracted by methylene chloride (MC), petroleum ether (PE), ethyl acetate (EtOAc) and butanol (B) solvents, each alone exhibited significant dose-dependent anti-proliferative activity on MCF7 and HepG2 cells with best results for EtOAc with IC 50 values 21.32 and 26.22 µg/ml, respectively, as compared to vehicle-treated cells. HPLC analysis revealed the presence of 14 components in EtOAc fraction with highest concentrations for linoleic acid (LA) and S-allylthiocysteine (SAC). EtOAc fraction inhibited cancer cells proliferation through induction of apoptosis (revealed by a significant increase in mRNA levels of apoptotic markers, Caspase 3 and Bax and a significant decrease in mRNA levels of the anti-apoptotic marker, Bcl2) and cell cycle arrest in G2/M phase (indicated by increase in number of MCF7 and HepG2 cells in this phase). Conclusions: These in vitro results suggest that garlic EtOAc fraction or its main component could be used as an adjuvant to anticancer drug or can help in the development of new anticancer drugs based on components of this fraction.
Garlic - A Natural Source of Cancer Preventive Compounds
2002
Several epidemiological observations and a number of laboratory studies have indicated anticarcinogenic potential of garlic, which has been traditionally used from time immemorial for varied human ailments in different parts of the globe. The anticarcinogenic properties of garlic have been attributed to a wide variety of chemical compounds identified to be present in garlic but most studies have focused on specific thioallyl constituents. Garlic components have been found to block covalent binding of carcinogens to DNA, enhance degradation of carcinogens, have antioxidative and free radical scavenging properties and to regulate cell proliferation, apoptosis and immune responses. In view of the variety of effects produced by garlic and its chemical constituents, renewed interest has been generated in investigating its medicinal properties, particularly with reference to cancer prevention and prophylaxis. There are a number of mechanisms at work which jointly are responsible for elici...
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),
Effects of aqueous garlic extract on oxidant/antioxidant status in 32 D and 32 Dp cell lines
Planta Medica, 2006
To investigate the possible effects of aqueous garlic extract on the oxidant/antioxidant status and apoptosis in 32D (wild type mouse myeloid cell = normal) and 32Dp210 (BCR-ABL fusion gene (+) mouse myeloid cell = Chronic Myelocytic Leukemia cells) cell lines. Materials and methods: Aqueous garlic extract (10% w/v) was added into the cell line media with 2 different final concentrations (0.4% and 1%). At 0 h and at 24, 48, and 72 h later, the oxidant (malondialdehyde (MDA) level, and xanthine oxidase (XO) enzyme activity) and antioxidant (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) enzyme activities) parameters were measured in the cell lines. Results: It was observed that the garlic extract caused no change in the XO and antioxidant enzyme activities, but it increased the MDA level in the 32D cell line. However, significant increases were found in the MDA level, XO, and antioxidant enzyme activities in the 32Dp210 cell line treated by the garlic extract. Additionally, it was shown that garlic extract had antiproliferative and apoptotic effects on both cell lines. The most effective apoptotic dose was found to be 0.4% (w/v), and at this concentration the death risk of the 32Dp210 cell line was calculated at 2.08 times higher than that of the 32D cell line. Conclusion: It has been suggested that garlic directly causes oxidant stress in the 32D cell line owing to its own oxidant ingredients, and that the oxidant stress created by garlic in the 32Dp210 cell line might occur through increased XO activity and/or its oxidant ingredients. Additionally, antioxidant enzyme activities were found to increase in the 32Dp210 cell line; it would seem that this compensatory change could not prevent the oxidant stress created. We think that the oxidant potential of garlic extract might play a part in its possible anticancer potential, previously supposed by several investigators.
Effects of aqueous garlic extract on oxidant/antioxidant status in 32D and 32Dp210 cell lines
Turkish Journal of Medical Sciences, 2010
To investigate the possible effects of aqueous garlic extract on the oxidant/antioxidant status and apoptosis in 32D (wild type mouse myeloid cell = normal) and 32Dp210 (BCR-ABL fusion gene (+) mouse myeloid cell = Chronic Myelocytic Leukemia cells) cell lines. Materials and methods: Aqueous garlic extract (10% w/v) was added into the cell line media with 2 different final concentrations (0.4% and 1%). At 0 h and at 24, 48, and 72 h later, the oxidant (malondialdehyde (MDA) level, and xanthine oxidase (XO) enzyme activity) and antioxidant (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) enzyme activities) parameters were measured in the cell lines. Results: It was observed that the garlic extract caused no change in the XO and antioxidant enzyme activities, but it increased the MDA level in the 32D cell line. However, significant increases were found in the MDA level, XO, and antioxidant enzyme activities in the 32Dp210 cell line treated by the garlic extract. Additionally, it was shown that garlic extract had antiproliferative and apoptotic effects on both cell lines. The most effective apoptotic dose was found to be 0.4% (w/v), and at this concentration the death risk of the 32Dp210 cell line was calculated at 2.08 times higher than that of the 32D cell line. Conclusion: It has been suggested that garlic directly causes oxidant stress in the 32D cell line owing to its own oxidant ingredients, and that the oxidant stress created by garlic in the 32Dp210 cell line might occur through increased XO activity and/or its oxidant ingredients. Additionally, antioxidant enzyme activities were found to increase in the 32Dp210 cell line; it would seem that this compensatory change could not prevent the oxidant stress created. We think that the oxidant potential of garlic extract might play a part in its possible anticancer potential, previously supposed by several investigators.