The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform

Kent S. Gates - One of the best experts on this subject based on the ideXlab platform.

  • Evidence for Thiol-Dependent Production of Oxygen Radicals by 4-Methyl-5-pyrazinyl-3H-1,2-dithiole-3-thione (Oltipraz) and 3H-1,2-Dithiole-3-thione: Possible Relevance to the Anticarcinogenic Properties of 1,2-Dithiole-3-thiones
    Chemical Research in Toxicology, 1997
    Co-Authors: Kent S. Gates
    Abstract:

    1,2-Dithiole-3-thiones are an important class of Anticarcinogens that selectively induce cellular production of chemoprotective phase II detoxification enzymes. It is important to identify chemical properties of Anticarcinogens that are responsible for this enzyme induction. Previously, the ability of 1,2-dithiole-3-thiones to induce phase II enzymes has been attributed to their electrophilic character. We report here that the Anticarcinogenic 1,2-dithiole-3-thiones, oltipraz (4-methyl-5-pyrazinyl-3H-1,2-dithiole-3-thione, 1) and 3H-1,2-dithiole-3-thione (2), in conjunction with thiols, including the biological thiol glutathione, mediate the conversion of molecular oxygen to reactive oxygen radicals. Using a plasmid-based assay that monitors DNA cleavage, we find that 1 and 2, at micromolar concentrations, efficiently cleave DNA and that this cleavage can be suppressed by removal of molecular oxygen, addition of radical scavenging agents (mannitol, methanol, ethanol, and dimethyl sulfoxide), chelators of adventitious trace metals, and the peroxide-destroying enzyme catalase. Taken together, our data suggest that, in these reactions, molecular oxygen is converted to a peroxide species that undergoes a trace metal-catalyzed, Fenton-type reaction to generate oxygen radicals that cleave DNA. Reactive oxygen species are known to be capable of modulating gene expression in mammalian cells; thus, our studies indicate that oxygen radical production by 1,2-dithiole-3-thiones should be considered as a second chemical property, in addition to electrophilicity, that may play a role in the induction of protective phase II enzymes by this promising class of Anticarcinogens.

Yang Yang - One of the best experts on this subject based on the ideXlab platform.

  • pterostilbene exerts anticancer activity on non small cell lung cancer via activating endoplasmic reticulum stress
    Scientific Reports, 2017
    Co-Authors: Yang Yang, Chongxi Fan, Dong Liu, Xiao Feng, Shuai Jiang, Zhigang Qin, Xiaolong Yan
    Abstract:

    Pterostilbene (PT), the natural dimethylated analog of resveratrol (RSV), is a potent Anticarcinogen for non-small-cell lung cancer (NSCLC), but its anti-NSCLC mechanisms remain unclear. In this study, we show that PT treatment time- and dose-dependently enhanced the endoplasmic reticulum stress (ERS) signaling (i.e., p-PERK, IRE1, ATF4, CHOP), thus decreasing the cell viability and inducing apoptosis in human PC9 and A549 NSCLC cell lines. Moreover, the decreased migratory and adhesive abilities, downregulation of intracellular glutathione (GSH) level, enhanced reactive oxygen species (ROS) generation, Caspase 3 activity and mitochondrial membrane depolarization were observed in NSCLC cells treated with PT. These effects were reversed by CHOP siRNA which inhibited the ERS signaling pathway, but were promoted by thapsigargin (a classical ERS inducer) in vitro. Besides, in vivo studies also verify that PT exerted anticancer activity by mobilizing ERS signaling and apoptosis-related proteins, and these effects were enhanced by thapsigargin. Therefore, ERS activation may represent a new mechanism of anti-NSCLC action by PT, and a novel therapeutic intervention for lung cancer.

  • melatonin as a potential Anticarcinogen for non small cell lung cancer
    Oncotarget, 2016
    Co-Authors: Yang Yang, Chongxi Fan, Jing Han, D H Wang, Dong Liu, Russel J Reiter, Xiaolong Yan
    Abstract:

    Non-small-cell lung cancer (NSCLC) is a leading cause of death from cancer worldwide. Melatonin, an indoleamine discovered in the pineal gland, exerts pleiotropic anticancer effects against a variety of cancer types. In particular, melatonin may be an important anticancer drug in the treatment of NSCLC. Herein, we review the correlation between the disruption of the melatonin rhythm and NSCLC incidence; we also evaluate the evidence related to the effects of melatonin in inhibiting lung carcinogenesis. Special focus is placed on the oncostatic effects of melatonin, including anti-proliferation, induction of apoptosis, inhibition of invasion and metastasis, and enhancement of immunomodulation. We suggest the drug synergy of melatonin with radio- or chemotherapy for NSCLC could prove to be useful. Taken together, the information complied herein may serve as a comprehensive reference for the anticancer mechanisms of melatonin against NSCLC, and may be helpful for the design of future experimental research and for advancing melatonin as a therapeutic agent for NSCLC.

Lynn M Rundhaugen - One of the best experts on this subject based on the ideXlab platform.

  • Structure-function relationships of the dietary Anticarcinogen ellagic acid
    Carcinogenesis, 1996
    Co-Authors: H. David, Lynn M Rundhaugen, N.sokalingum Pillay, Gary D. Stoner, William A. Rosche
    Abstract:

    Ellagic acid is a complex planar molecule which demonstrates a variety of Anticarcinogenic activities. Ellagic acid has been shown to inhibit the CYP1A1-dependent activation of benzo[a]pyrene ; to bind to and detoxify the diolepoxide of benzo[a]pyrene ; to bind to DNA and reduce the formation of O 6 -methylguanine by methylating carcinogens; and to induce the phase II detoxification enzymes glutathione S-transferase Ya and NAD(P)H :quinone reductase. Chemical analogs of ellagic acid were synthesized to examine the relationship between the hydroxyl and lactone groups of the ellagic acid molecule and its different Anticarcinogenic activities. These studies demonstrated that both the 3-hydroxyl and the 4-hydroxyl groups were required for ellagic acid to directly detoxify the diolepoxide of benzo[a]pyrene, while only the 4-hydroxyl groups were necessary for ellagic acid to inhibit CYP1A1-dependent benzo[a]pyrene hydroxylase activity. Induction of glutathione S-transferase Ya and NAD(P) :quinone reductase required the lactone groups of ellagic acid, but the hydroxyl groups were not required for the induction of these phase II enzymes. In addition, the lactone groups, but not the hydroxyl groups, were required for the analogs to reduce the carcinogen-induced formation of O 6 -methylguanine. Thus, different portions of the ellagic acid molecule are responsible for its different putative Anticarcinogenic activities.

  • ellagic acid induces nad p h quinone reductase through activation of the antioxidant responsive element of the rat nad p h quinone reductase gene
    Carcinogenesis, 1994
    Co-Authors: H. David, Lynn M Rundhaugen
    Abstract:

    Induction of cellular detoxification enzymes can increase detoxification of carcinogens and reduce carcinogeninduced mutagenesis and tumorigenesis. To determine if the dietary Anticarcinogen ellagic acid induced enzymes which detoxify xenobiotics and carcinogens, we examined the effect of ellagic acid on the expression of the phase II detoxification enzyme NAD(P)H:quinone reductase (QR). QR is induced by xenobiotics and antioxidants interacting with the xenobiotic responsive and antioxidant responsive elements of the 5' regulatory region of the QR gene. Ellagic acid is structurally related to the antioxidants which induce QR and we proposed that ellagic acid would induce QR expression through activation of the antioxidant responsive element of the QR gene

Xiaolong Yan - One of the best experts on this subject based on the ideXlab platform.

  • pterostilbene exerts anticancer activity on non small cell lung cancer via activating endoplasmic reticulum stress
    Scientific Reports, 2017
    Co-Authors: Yang Yang, Chongxi Fan, Dong Liu, Xiao Feng, Shuai Jiang, Zhigang Qin, Xiaolong Yan
    Abstract:

    Pterostilbene (PT), the natural dimethylated analog of resveratrol (RSV), is a potent Anticarcinogen for non-small-cell lung cancer (NSCLC), but its anti-NSCLC mechanisms remain unclear. In this study, we show that PT treatment time- and dose-dependently enhanced the endoplasmic reticulum stress (ERS) signaling (i.e., p-PERK, IRE1, ATF4, CHOP), thus decreasing the cell viability and inducing apoptosis in human PC9 and A549 NSCLC cell lines. Moreover, the decreased migratory and adhesive abilities, downregulation of intracellular glutathione (GSH) level, enhanced reactive oxygen species (ROS) generation, Caspase 3 activity and mitochondrial membrane depolarization were observed in NSCLC cells treated with PT. These effects were reversed by CHOP siRNA which inhibited the ERS signaling pathway, but were promoted by thapsigargin (a classical ERS inducer) in vitro. Besides, in vivo studies also verify that PT exerted anticancer activity by mobilizing ERS signaling and apoptosis-related proteins, and these effects were enhanced by thapsigargin. Therefore, ERS activation may represent a new mechanism of anti-NSCLC action by PT, and a novel therapeutic intervention for lung cancer.

  • melatonin as a potential Anticarcinogen for non small cell lung cancer
    Oncotarget, 2016
    Co-Authors: Yang Yang, Chongxi Fan, Jing Han, D H Wang, Dong Liu, Russel J Reiter, Xiaolong Yan
    Abstract:

    Non-small-cell lung cancer (NSCLC) is a leading cause of death from cancer worldwide. Melatonin, an indoleamine discovered in the pineal gland, exerts pleiotropic anticancer effects against a variety of cancer types. In particular, melatonin may be an important anticancer drug in the treatment of NSCLC. Herein, we review the correlation between the disruption of the melatonin rhythm and NSCLC incidence; we also evaluate the evidence related to the effects of melatonin in inhibiting lung carcinogenesis. Special focus is placed on the oncostatic effects of melatonin, including anti-proliferation, induction of apoptosis, inhibition of invasion and metastasis, and enhancement of immunomodulation. We suggest the drug synergy of melatonin with radio- or chemotherapy for NSCLC could prove to be useful. Taken together, the information complied herein may serve as a comprehensive reference for the anticancer mechanisms of melatonin against NSCLC, and may be helpful for the design of future experimental research and for advancing melatonin as a therapeutic agent for NSCLC.

H. David - One of the best experts on this subject based on the ideXlab platform.

  • Structure-function relationships of the dietary Anticarcinogen ellagic acid
    Carcinogenesis, 1996
    Co-Authors: H. David, Lynn M Rundhaugen, N.sokalingum Pillay, Gary D. Stoner, William A. Rosche
    Abstract:

    Ellagic acid is a complex planar molecule which demonstrates a variety of Anticarcinogenic activities. Ellagic acid has been shown to inhibit the CYP1A1-dependent activation of benzo[a]pyrene ; to bind to and detoxify the diolepoxide of benzo[a]pyrene ; to bind to DNA and reduce the formation of O 6 -methylguanine by methylating carcinogens; and to induce the phase II detoxification enzymes glutathione S-transferase Ya and NAD(P)H :quinone reductase. Chemical analogs of ellagic acid were synthesized to examine the relationship between the hydroxyl and lactone groups of the ellagic acid molecule and its different Anticarcinogenic activities. These studies demonstrated that both the 3-hydroxyl and the 4-hydroxyl groups were required for ellagic acid to directly detoxify the diolepoxide of benzo[a]pyrene, while only the 4-hydroxyl groups were necessary for ellagic acid to inhibit CYP1A1-dependent benzo[a]pyrene hydroxylase activity. Induction of glutathione S-transferase Ya and NAD(P) :quinone reductase required the lactone groups of ellagic acid, but the hydroxyl groups were not required for the induction of these phase II enzymes. In addition, the lactone groups, but not the hydroxyl groups, were required for the analogs to reduce the carcinogen-induced formation of O 6 -methylguanine. Thus, different portions of the ellagic acid molecule are responsible for its different putative Anticarcinogenic activities.

  • ellagic acid induces nad p h quinone reductase through activation of the antioxidant responsive element of the rat nad p h quinone reductase gene
    Carcinogenesis, 1994
    Co-Authors: H. David, Lynn M Rundhaugen
    Abstract:

    Induction of cellular detoxification enzymes can increase detoxification of carcinogens and reduce carcinogeninduced mutagenesis and tumorigenesis. To determine if the dietary Anticarcinogen ellagic acid induced enzymes which detoxify xenobiotics and carcinogens, we examined the effect of ellagic acid on the expression of the phase II detoxification enzyme NAD(P)H:quinone reductase (QR). QR is induced by xenobiotics and antioxidants interacting with the xenobiotic responsive and antioxidant responsive elements of the 5' regulatory region of the QR gene. Ellagic acid is structurally related to the antioxidants which induce QR and we proposed that ellagic acid would induce QR expression through activation of the antioxidant responsive element of the QR gene