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Shivendra V Singh - One of the best experts on this subject based on the ideXlab platform.

  • Running Title: Akt Inactivation in DATS-Induced Apoptosis
    2016
    Co-Authors: Dong Xiao, Shivendra V Singh
    Abstract:

    Diallyl Trisulfide, a constituent of processed garlic, inactivates Akt to trigger mitochondrial translocation of BAD and caspase-mediated apoptosis in human prostate cancer cell

  • prostate
    2016
    Co-Authors: Dong Xiao, Shivendra V Singh
    Abstract:

    Diallyl Trisulfide, a constituent of processed garlic, inactivates Akt to trigger mitochondrial translocation of BAD and caspase-mediated apoptosis in huma

  • abstract 3670 the role of reactive oxygen species in anticancer effects of Diallyl Trisulfide a bioactive component of garlic
    Cancer Research, 2013
    Co-Authors: Julie A Arlotti, Kumar Chandrakuntal, Shivendra V Singh
    Abstract:

    Diallyl Trisulfide (DATS) is a bioactive component of processed garlic with in vivo activity against chemically-induced as well as oncogene-driven cancer in rodent models. However, the mechanisms underlying anticancer effects of DATS (eg, growth inhibition, apoptosis induction, and suppression of migration in cancer cells) are not fully understood. The present study reveals a critical role for reactive oxygen species (ROS) in cellular anticancer responses to DATS. Exposure of human breast cancer cells (MDA-MB-231 and MCF-7) as well as a cell line derived from spontaneously developing mammary tumor of a MMTV-neu transgenic mouse (BRI-JM04) to DATS resulted in dose-dependent inhibition of cell viability and apoptosis induction. Interestingly, a non-tumorigenic normal human mammary cell line (MCF-10A) was resistant to growth inhibition and apoptosis induction by DATS. The DATS-induced apoptosis in MDA-MB-231, MCF-7, and BRI-JM04 cells was associated with ROS production as evidenced by fluorescence microscopy and flow cytometry using a chemical probe (MitoSOX Red). Ectopic expression of Cu,Zn-superoxide dismutase (Cu,Zn-SOD) as well as Mn-SOD conferred significant protection against DATS-induced ROS production and apoptotic cell death. The DATS treatment caused activation of Bax and Bak, and activation of Bak was nearly fully abolished by overexpression of Mn-SOD. Likewise, inhibition of MDA-MB-231 and MCF-7 cell migration resulting from DATS treatment was partially but statistically significantly attenuated by stable overexpression of Cu,Zn-SOD and Mn-SOD. This protection against inhibition of cell migration was attributable to abrogation of DATS-mediated induction of E-cadherin and suppression of vimentin. These results indicate that ROS play an important role in anticancer effects of DATS at least in human breast cancer cells. This study was supported by grant CA113363-07 awarded by the National Cancer Institute. Citation Format: Julie A. Arlotti, Kumar Chandra-Kuntal, Shivendra V. Singh. The role of reactive oxygen species in anticancer effects of Diallyl Trisulfide, a bioactive component of garlic. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3670. doi:10.1158/1538-7445.AM2013-3670

  • critical role for reactive oxygen species in apoptosis induction and cell migration inhibition by Diallyl Trisulfide a cancer chemopreventive component of garlic
    Breast Cancer Research and Treatment, 2013
    Co-Authors: Kumar Chandrakuntal, Joomin Lee, Shivendra V Singh
    Abstract:

    Diallyl Trisulfide (DATS) is a structurally simple but biologically active constituent of processed garlic with in vivo activity against chemically induced as well as oncogene-driven cancer in experimental rodents. This study offers novel insights into the mechanisms underlying anticancer effects of DATS using human breast cancer cells as a model. Exposure of human breast cancer cells (MCF-7 and MDA-MB-231) and a cell line derived from spontaneously developing mammary tumor of a transgenic mouse (BRI-JM04) to DATS resulted in a dose-dependent inhibition of cell viability that was accompanied by apoptosis induction. A non-tumorigenic normal human mammary cell line (MCF-10A) was resistant to growth inhibition and apoptosis induction by DATS. The DATS-induced apoptosis in MDA-MB-231, MCF-7, and BRI-JM04 cells was associated with reactive oxygen species (ROS) production as evidenced by fluorescence microscopy and flow cytometry using a chemical probe (MitoSOX Red). Overexpression of Cu,Zn-superoxide dismutase (Cu,Zn-SOD) as well as Mn-SOD conferred significant protection against DATS-induced ROS production and apoptotic cell death in MDA-MB-231 and MCF-7 cells. Activation of Bak, but not Bax, resulting from DATS treatment was markedly suppressed by overexpression of Mn-SOD. The DATS treatment caused ROS generation, but not activation of Bax or Bak, in MCF-10A cells. Furthermore, the DATS-mediated inhibition of cell migration was partially but significantly attenuated by Cu,Zn-SOD and Mn-SOD overexpression in association with changes in levels of proteins involved in epithelial–mesenchymal transition. The DATS-mediated induction of heme oxygenase-1 was partially attenuated by overexpression of Mn-SOD. These results provide novel mechanistic insights indicating a critical role for ROS in anticancer effects of DATS.

  • molecular mechanisms and targets of cancer chemoprevention by garlic derived bioactive compound Diallyl Trisulfide
    Indian Journal of Experimental Biology, 2011
    Co-Authors: Marie Lue Antony, Shivendra V Singh
    Abstract:

    Health benefits of garlic and other Allium vegetables (e.g., onions), such as lipid lowering and anticancer effects, are credited to metabolic byproducts, including Diallyl Trisulfide (DATS). Evidence for anticancer effects of garlic derives from both population-based case-control studies, and clinical and laboratory investigations using purified garlic constituents such as DATS. Studies have shown that DATS can offer protection against chemically-induced neoplasia as well as oncogene-driven spontaneous cancer development in experimental rodents. Mechanisms underlying cancer chemopreventive effects of DATS are not completely understood, but known pharmacological responses to this natural product include alteration in carcinogen-metabolizing enzymes, cell cycle arrest, induction of apoptotic cell death, suppression of oncogenic signal transduction pathways, and inhibition of neoangiogenesis. This article reviews mechanisms and targets of cancer chemoprevention by DATS.

Jing Gung Chung - One of the best experts on this subject based on the ideXlab platform.

  • Diallyl sulfide Diallyl disulfide and Diallyl Trisulfide inhibit migration and invasion in human colon cancer colo 205 cells through the inhibition of matrix metalloproteinase 2 7 and 9 expressions
    Environmental Toxicology, 2013
    Co-Authors: Kuang Chi Lai, Jing Gung Chung, Jai Sing Yang, Chao Lin Kuo, Shu Chun Hsu, Nou Ying Tang, Te Chun Hsia
    Abstract:

    Diallyl sulfide (DAS), Diallyl disulfide (DADS), and Diallyl Trisulfide (DATS) are major organosulfur compounds exiting in garlic (Allium sativum). These compounds are reported to exhibit various pharmacological properties such as antibacteria, antiangiogenesis, anticancer, and anticoagulation, and they also induce cytotoxicity and induction of apoptosis in human cancer cells. Although these compounds show wide spectrum of biological activities, there are no reports to show that DAS, DADS, and DATS affected migration and invasion of human colon cancer cells, and their exact molecular mechanisms are not well investigated. Therefore, the purpose of this study was to determine whether DAS, DADS, and DATS affected the invasion and migration abilities of colo 205 human colon cancer cells. The results indicate that DAS, DADS, and DATS at 10 and 25 μM inhibited the migration and invasion of colo 205 cells in the order of DATS < DADS < DAS. DATS is the highest for inhibition of migration and invasion of colo 205 cells. DAS, DADS, and DATS induce downregulation expression of PI3K, Ras, MEKK3, MKK7, ERK1/2, JNK1/2, and p38 and then lead to the inhibition of MMP-2, -7, and -9. DAS, DADS, and DATS inhibited NF-κB and COX-2 for leading to the inhibition of cell proliferation. Taken together, these results demonstrated that application of DAS, DADS, and DATS might serve as potential antimetastatic drugs.

  • Diallyl sulfide Diallyl disulfide and Diallyl Trisulfide inhibit migration and invasion in human colon cancer colo 205 cells through the inhibition of matrix metalloproteinase 2 7 and 9 expressions
    Environmental Toxicology, 2013
    Co-Authors: Kuang Chi Lai, Jing Gung Chung, Jai Sing Yang, Chao Lin Kuo, Shu Chun Hsu, Nou Ying Tang, Te Chun Hsia
    Abstract:

    Diallyl sulfide (DAS), Diallyl disulfide (DADS), and Diallyl Trisulfide (DATS) are major organosulfur compounds exiting in garlic (Allium sativum). These compounds are reported to exhibit various pharmacological properties such as antibacteria, antiangiogenesis, anticancer, and anticoagulation, and they also induce cytotoxicity and induction of apoptosis in human cancer cells. Although these compounds show wide spectrum of biological activities, there are no reports to show that DAS, DADS, and DATS affected migration and invasion of human colon cancer cells, and their exact molecular mechanisms are not well investigated. Therefore, the purpose of this study was to determine whether DAS, DADS, and DATS affected the invasion and migration abilities of colo 205 human colon cancer cells. The results indicate that DAS, DADS, and DATS at 10 and 25 μM inhibited the migration and invasion of colo 205 cells in the order of DATS < DADS < DAS. DATS is the highest for inhibition of migration and invasion of colo 205 cells. DAS, DADS, and DATS induce downregulation expression of PI3K, Ras, MEKK3, MKK7, ERK1/2, JNK1/2, and p38 and then lead to the inhibition of MMP-2, -7, and -9. DAS, DADS, and DATS inhibited NF-κB and COX-2 for leading to the inhibition of cell proliferation. Taken together, these results demonstrated that application of DAS, DADS, and DATS might serve as potential antimetastatic drugs. © 2011 Wiley Periodicals, Inc. Environ Toxicol 28: 479–488, 2013.

  • allicin induces p53 mediated autophagy in hep g2 human liver cancer cells
    Journal of Agricultural and Food Chemistry, 2012
    Co-Authors: Jing Gung Chung, Chitang Ho, Raghu Rajasekaran, Lee-yan Sheen
    Abstract:

    Garlic has been used throughout history for both culinary and medicinal purpose. Allicin is a major component of crushed garlic. Although it is sensitive to heat and light and easily metabolized into various compounds such as Diallyl disulfide, Diallyl Trisulfide, and Diallyl sulfide, allicin is still a major bioactive compound of crushed garlic. The mortality of hepatocellular carcinoma is quite high and ranks among the top 10 cancer-related deaths in Taiwan. Although numerous studies have shown the cancer-preventive properties of garlic and its components, there is no study on the effect of allicin on the growth of human liver cancer cells. In this study, we focused on allicin-induced autophagic cell death in human liver cancer Hep G2 cells. Our results indicated that allicin induced p53-mediated autophagy and inhibited the viability of human hepatocellular carcinoma cell lines. Using Western blotting, we observed that allicin decreased the level of cytoplasmic p53, the PI3K/mTOR signaling pathway, and ...

  • Diallyl sulfide Diallyl disulfide and Diallyl Trisulfide affect drug resistant gene expression in colo 205 human colon cancer cells in vitro and in vivo
    Phytomedicine, 2012
    Co-Authors: Kuang Chi Lai, Jai Sing Yang, Chao Lin Kuo, Hui Ying Huang, Fu Shin Chueh, Jing Gung Chung
    Abstract:

    To elevate chemo-resistance of human cancer cells is a major obstacle in the treatment and management of malignant cancers. Diallyl sulfide (DAS), Diallyl disulfide (DADS) and Diallyl Trisulfide (DATS) are presented in the Alliaceae family particularly in garlic. Although DAS, DADS and DATS have been shown to exhibit anticancer activities, there is little information on effects of these compounds on drug resistant genes in human colon cancer cells in vitro and in vivo. Herein, we are the first to show that DAS, DADS and DATS at 25 μM for 24-h and 48-h incubations promoted expression of drug resistant genes in colo 205 human colon cancer cells. In vitro experiments indicated that DATS promoted gene expression of multidrug resistant 1 (Mdr1) (p<0.05), and DAS and DADS promoted MRP3 gene expression and DATS alone stimulated gene expression of multidrug resistance-associated protein-1 (MRP1) (p<0.05) in colo 205 cells. In vivo studies demonstrated that DADS and DATS induced Mdr1 and MRP1 gene expression (p<0.05). DADS promoted MRP3 gene expression (p<0.05) as well as DADS and DATS increased MRP4 and MRP6 gene expression (p<0.05) in the colo 205 xenograft mice. Based on our in vitro and in vivo results, Diallyl polysulfides (DAS, DADS and DATS) affected the gene expression of the multidrug resistance in colo 205 human colon cancer cells in vitro and in vivo.

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

  • downregulation of chitin synthase a gene by Diallyl Trisulfide an active substance from garlic essential oil inhibits oviposition and alters the morphology of adult sitotroga cerealella
    Journal of Pest Science, 2020
    Co-Authors: Sakhawat Shah, Susu Zhang, Muhammad Hafeez, Muhammad Ilyas, Fenglian Yang
    Abstract:

    The Angoumois grain moth, Sitotroga cerealella Olivier (Lepidoptera: Gelechiidae), is the most serious and destructive pest of stored commodities around the globe, particularly on wheat, rice and maize. Previously, we confirmed that Diallyl Trisulfide (DAT), an active substance from garlic essential oil, reduced oviposition of females after a fumigation at the sublethal concentration (LC20 = 0.015 µL/L); meanwhile, through transcriptome sequencing, we found that DAT significantly downregulates the expression of chitin synthase A (CHSA) gene. To gain a broader insight, we assessed effects of DAT and dsRNA of CHSA gene of S. cerealella (dsScerCHSA) on the morphology, physiology and oviposition of adult S. cerealella, and we found that ScerCHSA was expressed in the adult stage and observed higher in the cuticle. Furthermore, results indicated that DAT fumigation significantly downregulated the mRNA expression of ScerCHSA and inhibited moth oviposition at the sublethal concentration. Downregulation of ScerCHSA resulted in chitin reduction, epidermal disruption, morphological and physiological alterations. Meanwhile, silencing of ScerCHSA resulted in the oviposition reduction of the moth; moreover, the morphological and physiological alterations were similar to the group treated with DAT. Therefore, we conclude that DAT could regulate the expression of ScerCHSA at the transcriptional level, cause histological and morphological alteration and finally inhibit the moth oviposition, which proves DAT possesses the great potential for being used in pest control as a friendly biopesticide.

  • effects of Diallyl Trisulfide an active substance from garlic essential oil on energy metabolism in male moth sitotroga cerealella olivier
    Insects, 2020
    Co-Authors: Yiyi Ying, Susu Zhang, Wenhan Yan, Yuchen Yao, Sakhawat Shah, Fenglian Yang
    Abstract:

    This study investigated the effects of Diallyl Trisulfide (DAT), an active substance from garlic essential oil, on the metabolism of the main energy substances of pre- and postmating males of Sitotroga cerealella. Males at 12 h postemergence were fumigated with DAT at a concentration (LC10 = 0.010 µL/L) in a glass jar for 7 h. The main energy metabolites from pre- and postmating males were determined, including protein, triglyceride, glycogen, total soluble sugar, trehalose, and trehalase. The contents of total protein and total soluble sugar and the trehalase activity of premating males were significantly increased following DAT treatment, whereas the contents of protein from the accessory gland, triglyceride, glycogen, and trehalose were significantly decreased after treatment. Additionally, after mating, the total protein and soluble sugar contents were significantly increased and the glycogen content was significantly decreased in the treatment group relative to the levels in controls, but there was no significant difference observed in triglyceride, accessory gland proteins, trehalose content, or trehalase activity between the treatment and control groups. Furthermore, the changes in the main energy substances between pre- and postmating in males after the DAT treatment (∆DAT) were smaller than those in the control group (∆CK). This result indicated that DAT can accelerate the rate of metabolism in males at LC10, leading to the accumulation of greater levels of total soluble sugar to support life activities and to the increased synthesis of proteins to resist an adverse environment.

  • effect of Diallyl Trisulfide on the reproductive behavior of the grain moth sitotroga cerealella lepidoptera gelechiidae
    Insects, 2019
    Co-Authors: Mengmeng Chang, Sakhawat Shah, Susu Zhang, Fenglian Yang
    Abstract:

    The Angoumois grain moth, Sitotroga cerealella (Olivier, 1789) (Lepidoptera: Gelechiidae), is primarily a pest of stored products, that feeds inside the grain as larvae inducing significant economic loss in various stored commodities. Our previous studies proved that garlic essential oil and its active substances inhibit oviposition in moths. To further explore the effect on reproductive behavior and accurately interpret the results in terms of effective control of the moth population, moths were treated with Diallyl Trisulfide (DATS), an active substance of garlic essential oil, at a dose of 0.015 µL/L in air (LC20, sub-lethal concentration). The results showed that fecundity and the proportion of viable eggs significantly decreased when the moths were treated with LC20 DATS. Furthermore, female circadian mating rhythms and calling periodicity changed significantly after treatment. Compared with controls, the peak in mating occurred approximately 1 h earlier on the first day after DATS treatment, while it was significantly later on days 2 and 3. Moreover, mating frequency declined in presence of DATS compared with the controls. The percentage of females engaging in calling behavior decreased significantly with time, to less than 50%, 2 days after treatment, while a high calling percentage (>80%) was recorded for control moths on all 4 days. In addition, DATS had an inhibitory effect on the mating duration of S. cerealella. Moreover, a significant reduction was observed in the amount of sex pheromones extracted 8 h and 9 h after treatment. Our findings suggested that DATS has the potential to manipulate the moth population at LC20 and would be an efficient alternative to synthetic insecticides for the control of pests having low toxicity to non-target organisms and ecosystems.

  • comparative transcriptome analysis reveals potential gene targets for ovipositional inhibition by Diallyl Trisulfide against female sitotroga cerealella
    Agri Gene, 2017
    Co-Authors: Yiyi Ying, Chaoliang Lei, Fenglian Yang
    Abstract:

    The angoumois grain moth, Sitotroga cerealella Olivier, is a serious stored-grain pest worldwide. In previous studies, we demonstrated that Diallyl Trisulfide (DATS), one of active substances from garlic essential oil, inhibited oviposition of S. cerealella, but the mechanism for this inhibition remains unclear. We suspected that DATS-regulated gene expression changes in S. cerealella may be a reason for the modulation of fertility and reproductive behaviors of the moth. Comparative transcriptomes of female S. cerealella were built by RNA-sequencing to detect differences between DATS exposure and background air with special lights on the key genes related to the fecundity. A total of 304 differentially expressed genes (DEGs) were detected in female moth after exposure to DATS, of which 120 were up-regulated, and 184 were down-regulated. Sixty-two of these DEGs encoding proteins involved in growth and development of eggs and regulation of hormones and mating behavior were identified, and of these, 49 were annotated as chorion protein. Meanwhile, quantitative real-time PCR verified that DEG data were reliable for further transcriptional analysis. Additionally, the results of ovarian dissection and oviposition activity bioassay suggest that DATS has negative effects on ovarian development and fecundity of S. cerealella. Our comprehensive sequence resource with desirable quality enriched the genomic platform of S. cerealella, and the DEGs that were identified will facilitate understanding of the molecular mechanism of ovipositional inhibition by DATS.

  • insecticidal activities of garlic substances against adults of grain moth sitotroga cerealella lepidoptera gelechiidae
    Insect Science, 2012
    Co-Authors: Fenglian Yang
    Abstract:

    The angoumois grain moth, Sitotroga cerealella (Olivier), is one of the most serious stored grain pests around the world. In attempts to reduce the losses caused by the moth and to suppress its populations, the fumigant activities, behavioral influence and ovipositional inhibition of garlic (Allium sativum) essential oil and its two major components, Diallyl disulfide and Diallyl Trisulfide, were investigated against the adult grain moth. Their effects on reduction in survival of first instar larvae to adult emergence were also evaluated. Results showed that these three materials (garlic essential oil, Diallyl disulfide and Diallyl Trisulfide) had significant fumigant activity with 50% lethal concentration values at 1.33, 0.99, and 1.02 μL/L air space, respectively; meanwhile, the three materials possessed high behavioral deterrent activities against adults in the Y-tube olfactometer. When applied to rice grains, these materials reduced adult longevity and inhibited oviposition, with ovipositional inhibition above 70% at a concentration of 1.5 μL/25 g in either no-choice or two-choice tests. In short, the study showed that both Diallyl disulfide and Diallyl Trisulfide, like garlic essential oil, acted as fumigants, produced behavioral deterrence and inhibited oviposition against angoumois grain moth. Our work here indicates that Diallyl disulfide and Diallyl Trisulfide may serve as potential alternatives for grain protectants since both of them can be prepared easily from readily available chemicals.

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

  • Diallyl Trisulfide induced g2 m phase cell cycle arrest in du145 cells is associated with delayed nuclear translocation of cyclin dependent kinase 1
    Pharmaceutical Research, 2010
    Co-Authors: Anna Hermanantosiewicz, Dong Xiao, Youngae Kim, Suhyeong Kim, Shivendra V Singh
    Abstract:

    Purpose The present study was undertaken to gain insight into the molecular mechanism of G2/M phase cell cycle arrest resulting from treatment of DU145 cells with Diallyl Trisulfide (DATS), a promising cancer chemopreventive constituent of garlic.

  • activation of a novel ataxia telangiectasia mutated and rad3 related checkpoint kinase 1 dependent prometaphase checkpoint in cancer cells by Diallyl Trisulfide a promising cancer chemopreventive constituent of processed garlic
    Molecular Cancer Therapeutics, 2007
    Co-Authors: Anna Hermanantosiewicz, Silvia D Stan, Eunryeong Hahm, Dong Xiao, Shivendra V Singh
    Abstract:

    Diallyl Trisulfide (DATS), a cancer chemopreventive constituent of garlic, inhibits growth of cancer cells by interfering with cell cycle progression, but the mechanism is not fully understood. Here, we show the existence of a novel ataxia-telangiectasia mutated and Rad3 related (ATR)/checkpoint kinase 1 (Chk1)-dependent checkpoint partially responsible for DATS-mediated prometaphase arrest in cancer cells, which is different from the recently described gamma irradiation-induced mitotic exit checkpoint. The PC-3 human prostate cancer cells synchronized in prometaphase by nocodazole treatment and released to DATS-containing medium remained arrested in prometaphase, whereas the cells released to normal medium exited mitosis and resumed cell cycle. The mitotic arrest was maintained even after 4 h of culture of DATS-treated cells (4-h treatment) in drug-free medium. The DATS-arrested mitotic cells exhibited accumulation of anaphase-promoting complex/cyclosome (APC/C) substrates cyclin A and cyclin B1 and hyperphosphorylation of securin, which was accompanied by increased phosphorylation of the APC/C regulatory subunits Cdc20 and Cdh1. The DATS-mediated accumulation of cyclin B1 and hyperphosphorylation of securin, Cdc20, and Cdh1 were partially but markedly attenuated by knockdown of Chk1 or ATR protein. The U2OS osteosarcoma cells expressing doxycycline-inducible kinase dead ATR were significantly more resistant not only to DATS-mediated prometaphase arrest but also to the accumulation of cyclin B1 and hyperphosphorylation of securin, Cdc20, and Cdh1 compared with cells expressing wild-type ATR. However, securin protein knockdown failed to rescue cells from DATS-induced prometaphase arrest. In conclusion, the present study describes a novel signaling pathway involving ATR/Chk1 in the regulation of DATS-induced prometaphase arrest.

  • c jun nh 2 terminal kinase signaling axis regulates Diallyl Trisulfide induced generation of reactive oxygen species and cell cycle arrest in human prostate cancer cells
    Cancer Research, 2006
    Co-Authors: Jedrzej Antosiewicz, Anna Hermanantosiewicz, Stanley W Marynowski, Shivendra V Singh
    Abstract:

    We have shown previously that generation of reactive oxygen species (ROS) is a critical event in G(2)-M phase cell cycle arrest caused by Diallyl Trisulfide (DATS), which is a highly promising anticancer constituent of processed garlic. Using DU145 and PC-3 human prostate cancer cells as a model, we now report a novel mechanism involving c-Jun NH(2)-terminal kinase (JNK) signaling axis, which is known for its role in regulation of cell survival and apoptosis, in DATS-induced ROS production. The DATS-induced ROS generation, G(2)-M phase cell cycle arrest and degradation, and hyperphosphorylation of Cdc25C were significantly attenuated in the presence of EUK134, a combined mimetic of superoxide dismutase and catalase. Interestingly, the DATS-induced ROS generation and G(2)-M phase cell cycle arrest were also inhibited significantly in the presence of desferrioxamine, an iron chelator, but this protection was not observed with iron-saturated desferrioxamine. DATS treatment caused a marked increase in the level of labile iron that was accompanied by degradation of light chain of iron storage protein ferritin. Interestingly, DATS-mediated degradation of ferritin, increase in labile iron pool, ROS generation, and/or cell cycle arrest were significantly attenuated by ectopic expression of a catalytically inactive mutant of JNK kinase 2 and RNA interference of stress-activated protein kinase/extracellular signal-regulated kinase 1 (SEK1), upstream kinases in JNK signal transduction pathway. In conclusion, the present study provides experimental evidence to indicate existence of a novel pathway involving JNK signaling axis in regulation of DATS-induced ROS generation.

  • Diallyl Trisulfide induced g2 m phase cell cycle arrest in human prostate cancer cells is caused by reactive oxygen species dependent destruction and hyperphosphorylation of cdc25c
    Oncogene, 2005
    Co-Authors: Dong Xiao, Anna Hermanantosiewicz, Jedrzej Antosiewicz, Hui Xiao, Marni Brisson, John S Lazo, Shivendra V Singh
    Abstract:

    Diallyl Trisulfide-induced G 2 –M phase cell cycle arrest in human prostate cancer cells is caused by reactive oxygen species-dependent destruction and hyperphosphorylation of Cdc25C

  • Diallyl Trisulfide induced g2 m phase cell cycle arrest in human prostate cancer cells is caused by reactive oxygen species dependent destruction and hyperphosphorylation of cdc25c
    Oncogene, 2005
    Co-Authors: Dong Xiao, Anna Hermanantosiewicz, Jedrzej Antosiewicz, Hui Xiao, Marni Brisson, John S Lazo, Shivendra V Singh
    Abstract:

    Molecular mechanism of cell cycle arrest caused by Diallyl Trisulfide (DATS), a garlic-derived cancer chemopreventive agent, has been investigated using PC-3 and DU145 human prostate cancer cells as a model. Treatment of PC-3 and DU145 cells, but not a normal prostate epithelial cell line (PrEC), with growth suppressive concentrations of DATS caused enrichment of the G2–M fraction. The DATS-induced cell cycle arrest in PC-3 cells was associated with increased Tyr15 phosphorylation of cyclin-dependent kinase 1 (Cdk1) and inhibition of Cdk1/cyclinB1 kinase activity. The DATS-treated PC-3 and DU145 cells also exhibited a decrease in the protein level of Cdc25C and an increase in its Ser216 phosphorylation. The DATS-mediated decrease in protein level and Ser216 phosphorylation of Cdc25C as well as G2–M phase cell cycle arrest were significantly attenuated in the presence of N-acetylcysteine implicating reactive oxygen species (ROS) in cell cycle arrest caused by DATS. ROS generation was observed in DATS-treated PC-3 and DU145 cells. DATS treatment also caused an increase in the protein level of Cdk inhibitor p21, but DATS-induced G2–M phase arrest was not affected by antisense-mediated suppression of p21 protein level. In conclusion, the results of the present study indicate that DATS-induced G2–M phase cell cycle arrest in human prostate cancer cells is caused by ROS-mediated destruction and hyperphosphorylation of Cdc25C.

Kuang Chi Lai - One of the best experts on this subject based on the ideXlab platform.

  • Diallyl sulfide Diallyl disulfide and Diallyl Trisulfide inhibit migration and invasion in human colon cancer colo 205 cells through the inhibition of matrix metalloproteinase 2 7 and 9 expressions
    Environmental Toxicology, 2013
    Co-Authors: Kuang Chi Lai, Jing Gung Chung, Jai Sing Yang, Chao Lin Kuo, Shu Chun Hsu, Nou Ying Tang, Te Chun Hsia
    Abstract:

    Diallyl sulfide (DAS), Diallyl disulfide (DADS), and Diallyl Trisulfide (DATS) are major organosulfur compounds exiting in garlic (Allium sativum). These compounds are reported to exhibit various pharmacological properties such as antibacteria, antiangiogenesis, anticancer, and anticoagulation, and they also induce cytotoxicity and induction of apoptosis in human cancer cells. Although these compounds show wide spectrum of biological activities, there are no reports to show that DAS, DADS, and DATS affected migration and invasion of human colon cancer cells, and their exact molecular mechanisms are not well investigated. Therefore, the purpose of this study was to determine whether DAS, DADS, and DATS affected the invasion and migration abilities of colo 205 human colon cancer cells. The results indicate that DAS, DADS, and DATS at 10 and 25 μM inhibited the migration and invasion of colo 205 cells in the order of DATS < DADS < DAS. DATS is the highest for inhibition of migration and invasion of colo 205 cells. DAS, DADS, and DATS induce downregulation expression of PI3K, Ras, MEKK3, MKK7, ERK1/2, JNK1/2, and p38 and then lead to the inhibition of MMP-2, -7, and -9. DAS, DADS, and DATS inhibited NF-κB and COX-2 for leading to the inhibition of cell proliferation. Taken together, these results demonstrated that application of DAS, DADS, and DATS might serve as potential antimetastatic drugs. © 2011 Wiley Periodicals, Inc. Environ Toxicol 28: 479–488, 2013.

  • Diallyl sulfide Diallyl disulfide and Diallyl Trisulfide inhibit migration and invasion in human colon cancer colo 205 cells through the inhibition of matrix metalloproteinase 2 7 and 9 expressions
    Environmental Toxicology, 2013
    Co-Authors: Kuang Chi Lai, Jing Gung Chung, Jai Sing Yang, Chao Lin Kuo, Shu Chun Hsu, Nou Ying Tang, Te Chun Hsia
    Abstract:

    Diallyl sulfide (DAS), Diallyl disulfide (DADS), and Diallyl Trisulfide (DATS) are major organosulfur compounds exiting in garlic (Allium sativum). These compounds are reported to exhibit various pharmacological properties such as antibacteria, antiangiogenesis, anticancer, and anticoagulation, and they also induce cytotoxicity and induction of apoptosis in human cancer cells. Although these compounds show wide spectrum of biological activities, there are no reports to show that DAS, DADS, and DATS affected migration and invasion of human colon cancer cells, and their exact molecular mechanisms are not well investigated. Therefore, the purpose of this study was to determine whether DAS, DADS, and DATS affected the invasion and migration abilities of colo 205 human colon cancer cells. The results indicate that DAS, DADS, and DATS at 10 and 25 μM inhibited the migration and invasion of colo 205 cells in the order of DATS < DADS < DAS. DATS is the highest for inhibition of migration and invasion of colo 205 cells. DAS, DADS, and DATS induce downregulation expression of PI3K, Ras, MEKK3, MKK7, ERK1/2, JNK1/2, and p38 and then lead to the inhibition of MMP-2, -7, and -9. DAS, DADS, and DATS inhibited NF-κB and COX-2 for leading to the inhibition of cell proliferation. Taken together, these results demonstrated that application of DAS, DADS, and DATS might serve as potential antimetastatic drugs.

  • Diallyl sulfide Diallyl disulfide and Diallyl Trisulfide affect drug resistant gene expression in colo 205 human colon cancer cells in vitro and in vivo
    Phytomedicine, 2012
    Co-Authors: Kuang Chi Lai, Jai Sing Yang, Chao Lin Kuo, Hui Ying Huang, Fu Shin Chueh, Jing Gung Chung
    Abstract:

    To elevate chemo-resistance of human cancer cells is a major obstacle in the treatment and management of malignant cancers. Diallyl sulfide (DAS), Diallyl disulfide (DADS) and Diallyl Trisulfide (DATS) are presented in the Alliaceae family particularly in garlic. Although DAS, DADS and DATS have been shown to exhibit anticancer activities, there is little information on effects of these compounds on drug resistant genes in human colon cancer cells in vitro and in vivo. Herein, we are the first to show that DAS, DADS and DATS at 25 μM for 24-h and 48-h incubations promoted expression of drug resistant genes in colo 205 human colon cancer cells. In vitro experiments indicated that DATS promoted gene expression of multidrug resistant 1 (Mdr1) (p<0.05), and DAS and DADS promoted MRP3 gene expression and DATS alone stimulated gene expression of multidrug resistance-associated protein-1 (MRP1) (p<0.05) in colo 205 cells. In vivo studies demonstrated that DADS and DATS induced Mdr1 and MRP1 gene expression (p<0.05). DADS promoted MRP3 gene expression (p<0.05) as well as DADS and DATS increased MRP4 and MRP6 gene expression (p<0.05) in the colo 205 xenograft mice. Based on our in vitro and in vivo results, Diallyl polysulfides (DAS, DADS and DATS) affected the gene expression of the multidrug resistance in colo 205 human colon cancer cells in vitro and in vivo.