Impact of JNK1, JNK2, and ligase Itch on reactive oxygen species formation and survival of prostate cancer cells treated with diallyl trisulfide

Sielicka-Dudzin, Alicja; Borkowska, Andzelika; Herman-Antosiewicz, Anna; Woźniak, Michał; Jóźwik, Agnieszka; Fedeli, Donatella; Antosiewicz, Jędrzej

doi:10.1007/s00394-011-0241-0

Cited by 17 publications

(12 citation statements)

References 33 publications

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“…The mechanism by which DATS causes ROS production has been investigated previously and involves elevation of labile iron pool due to ferritin degradation in an c-jun NH 2 -terminal kinase-dependent manner [36–38]. A role for the adapter protein p66Shc in DATS-induced ROS production was also demonstrated recently [37].…”

Section: Discussionmentioning

confidence: 98%

Critical role for reactive oxygen species in apoptosis induction and cell migration inhibition by diallyl trisulfide, a cancer chemopreventive component of garlic

Chandra-Kuntal

Lee

Singh

2013

Breast Cancer Res Treat

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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. The present 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, respectively) 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.

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Section: Discussionmentioning

confidence: 98%

Critical role for reactive oxygen species in apoptosis induction and cell migration inhibition by diallyl trisulfide, a cancer chemopreventive component of garlic

Chandra-Kuntal

Lee

Singh

2013

Breast Cancer Res Treat

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“…First of all, we observed that DATS-induced ferritin H degradation was significantly attenuated in PNT1a cells. In the case of ferritin L we did observe a small increase in the level of this protein in PNT1A cells, whereas as reported before, in PC-3 cells a significant decrease was observed (6). A downregulation of ferritin level by increased degradation or decreased biosynthesis of the protein leads to the elevation of labile iron pool (15).…”

Section: Discussionmentioning

confidence: 66%

“…We demonstrated that DATS treatment led to JNK-dependent phosphorylation and activation of p66Shc, and ligase Itch. The activation of this signaling pathway leads to ferritin degradation, an increase in LIP and iron-dependent ROS formation (6,7). Therefore one of the goals of this study was to evaluate if such signaling pathways would be activated in noncancerous prostate cell line after DATS treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, we demonstrated that ferritin degradation was mediated by c-jun terminal kinase 1 (JNK1) and ubiquitin ligase 3 Itch. Cells expressing plasmids encoding inactive form of JNK1 or Itch were shown to be completely resistant to DATS induced ferritin degradation (6). In addition to that, we observed that in prostate cancer cells ferritin degradation was mediated by the adaptor protein p66Shc phosphorylated at serine 36.…”

Section: Introductionmentioning

confidence: 89%

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Diallyl Trisulfide Is More Cytotoxic to Prostate Cancer Cells PC-3 than to Noncancerous Epithelial Cell Line PNT1A: A Possible Role of p66Shc signaling Axis

Borkowska

Knap

Antosiewicz

2013

Nutrition and Cancer

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Diallyl trisulfide (DATS) is an organosulfur compound isolated from garlic, and has been shown to have anticancer activity both in vitro and in vivo. The aim of this study was to compare cytotoxic effects of DATS on prostate cancer cells PC-3 and noncancerous human prostate epithelial cells PNT1A. PC-3 prostate cancer and noncancerous human prostate epithelial cells PNT1A were used in the study. We observed that PNT1A cells had higher resistance to DATS-induced cell death than PC-3 cells. Investigating signaling pathways involved in the cell death we observed that p66Shc phosphorylation at serine 36 and extracellular signal-regulated kinase 1/2 activation induced by DATS, were significantly attenuated in PNT1A cells as compared to PC-3 cells. Moreover, DATS-induced Akt inactivation was also significantly reduced in PNT1A cells. In addition to that, DATS-induced reactive oxygen species generation was nearly completely abolished in PNT1A cells. Interestingly, DATS induced only slight decrease in the level of ferritin H, whereas ferritin L was elevated. These data suggest that cytotoxicity of DATS toward PNT1A cells is strongly reduced as opposed to PC-3 cancer cells, which corresponds to the lower activation of prodeath signaling pathway mediated by the adaptor protein p66Shc in the noncancerous PNT1A cells.

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“…DATS has been shown to induce cell cycle arrest by enhancing generation of reactive oxygen species (ROS) [ 33 , 34 , 43 , 45 , 47 ]. One pathway of ROS generation begins with degradation of the iron storage protein ferritin, which has been shown following DATS treatment, leading to an increase in labile iron pool (LIP) size [ 43 , 47 , 48 ]. Then, through the Fenton/Haber-Weiss reaction, free ferric iron reacts with superoxide and hydrogen peroxide to form hydroxyl radicals and hydroxide ions [ 34 , 49 ].…”

Section: Mechanisms Of Actionmentioning

confidence: 99%

Dietary Bioactive Diallyl Trisulfide in Cancer Prevention and Treatment

Puccinelli

Stan

2017

IJMS

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Bioactive dietary agents have been shown to regulate multiple cancer hallmark pathways. Epidemiologic studies have linked consumption of Allium vegetables, such as garlic and onions, to decreased incidence of cancer. Diallyl trisulfide (DATS), a bioactive compound derived from Allium vegetables, has been investigated as an anti-cancer and chemopreventive agent. Preclinical studies provide ample evidence that DATS regulates multiple cancer hallmark pathways including cell cycle, apoptosis, angiogenesis, invasion, and metastasis. DATS has been shown to arrest cancer cells at multiple stages of the cell cycle with the G2/M arrest being the most widely reported. Additionally, increased pro-apoptotic capacity as a result of regulating intrinsic and extrinsic apoptotic pathway components has been widely reported following DATS treatment. Invasion, migration, and angiogenesis represent emerging targets of DATS and support its anti-cancer properties. This review summarizes DATS mechanisms of action as an anti-cancer and chemopreventive agent. These studies provide rationale for future investigation into its use as a cancer chemopreventive agent.

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Impact of JNK1, JNK2, and ligase Itch on reactive oxygen species formation and survival of prostate cancer cells treated with diallyl trisulfide

Abstract: These results suggest that JNK1-dependent increase in LIP is mediated by Itch ubiquitin ligase.

Cited by 17 publications

References 33 publications

Critical role for reactive oxygen species in apoptosis induction and cell migration inhibition by diallyl trisulfide, a cancer chemopreventive component of garlic

Critical role for reactive oxygen species in apoptosis induction and cell migration inhibition by diallyl trisulfide, a cancer chemopreventive component of garlic

Diallyl Trisulfide Is More Cytotoxic to Prostate Cancer Cells PC-3 than to Noncancerous Epithelial Cell Line PNT1A: A Possible Role of p66Shc signaling Axis

Dietary Bioactive Diallyl Trisulfide in Cancer Prevention and Treatment

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