Differential responses from seven mammalian cell lines to the treatments of detoxifying enzyme inducers

Jiang, Zhen; Chen, Chi; Yang, Bo; Hebbar, Vidya; Kong, Ah Ng Tony

doi:10.1016/s0024-3205(03)00101-2

Cited by 85 publications

(49 citation statements)

References 22 publications

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“…The increase in expressions and activities of these phase II enzymes was also observed in vitro. SFN induced GSTA1/2 and GSTP1 mRNA in primary rat hepatocytes, induced GSTA1/2 and GSTM1 mRNA in primary human hepatocytes (22), and increased GST and NQO1 activities in murine HepG1c1c7 cells (39,40). SFN also induced phase II genes in other cell lines (colon and prostate).…”

Section: Induction Of Phase II Dmesmentioning

confidence: 99%

Molecular Targets of Dietary Phenethyl Isothiocyanate and Sulforaphane for Cancer Chemoprevention

Cheung

Kong

2009

AAPS J

328

289

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Abstract. Development of cancer is a long-term and multistep process which comprises initiation, progression, and promotion stages of carcinogenesis. Conceivably, it can be targeted and interrupted along these different stages. In this context, many naturally occurring dietary compounds from our daily consumption of fruits and vegetables have been shown to possess cancer preventive effects. Phenethyl isothiocyanate (PEITC) and sulforaphane (SFN) are two of the most widely investigated isothiocyanates from the crucifers. Both have been found to be very potent chemopreventive agents in numerous animal carcinogenesis models as well as cell culture models. They exert their chemopreventive effects through regulation of diverse molecular mechanisms. In this review, we will discuss the molecular targets of PEITC and SFN potentially involved in cancer chemoprevention. These include the regulation of drugmetabolizing enzymes phase I cytochrome P450s and phase II metabolizing enzymes. In addition, the signaling pathways including Nrf2-Keap 1, anti-inflammatory NFκB, apoptosis, and cell cycle arrest as well as some receptors will also be discussed. Furthermore, we will also discuss the similarities and their potential differences in the regulation of these molecular targets by PEITC and SFN.

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Section: Induction Of Phase II Dmesmentioning

confidence: 99%

Molecular Targets of Dietary Phenethyl Isothiocyanate and Sulforaphane for Cancer Chemoprevention

Cheung

Kong

2009

AAPS J

328

289

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“…In human HepG2 cells, for example, SFN increases mRNA of UDP-glucuronosyltranferase (UGT) 1A1 and GSTA1 [7], increases QR activity [11], and increases UGT1A1 protein as well as bilirubin glucuronidation [12]. An increase in GST and QR activities also was observed with SFN treatment in murine Hepa1c1c7 cells [11,13]. Whereas there was an apparent decrease in GST activity in HT29 cells, undifferentiated CaCo-2 cells demonstrated a dose-and time-dependent induction of GSTA1 and UGT1A1 upon SFN administration [14].…”

Section: Modulation Of Phase 2 Enzymesmentioning

confidence: 99%

Chemoprotection by sulforaphane: Keep one eye beyond Keap1

2006

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Sulforaphane (SFN) is an isothiocyanate found in cruciferous vegetables, with particularly high levels detected in broccoli and broccoli sprouts. Over a decade ago, this phytochemical was identified as a likely chemopreventive agent based on its ability to induce Phase 2 detoxification enzymes, as well as to inhibit Phase 1 enzymes involved in carcinogen activation. Considerable attention has focused on SFN as a 'blocking' agent, with the ability to modulate the Nrf2/Keap1 pathway, but recent evidence suggests that SFN acts by numerous other mechanisms. SFN induces cell cycle arrest and apoptosis in cancer cells, inhibits tubulin polymerization, activates checkpoint 2 kinase, and inhibits histone deacetylase activity. The latter findings suggest that SFN may be effective during the postinitiation stages of carcinogenesis, as a 'suppressing' agent. Moreover, pharmacological administration of SFN may be a promising therapeutic approach to the treatment of cancers, including those characterized by increased inflammation and involving viral or bacterial-related pathologies. The present review discusses the more widely established chemoprotective mechanisms of SFN, but makes the case for additional work on mechanisms that might be of importance during later stages of carcinogenesis, beyond Keap1.

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“…Jiang et al (35) have assessed phase II enzyme induction in seven cell lines in response to sulforaphane and other chemopreventive agents, reporting that Hepa 1c1c7 cells were highly inducible, but that others, including MCF-7 and MDA-MB-231 breast cancer cells, were poorly responsive to chemopreventive agents (e.g., sulforophane induced NQO1 2-fold in Hepa 1c1c7 cells, but <1.2-fold in MCF-7 cells). Background NQO1 activity was observed to be significantly higher in MCF-7 than in Hepa 1c1c7 cells (data not shown).…”

Section: Induction Of Nqo1in Breast Cancer Cellsmentioning

confidence: 99%

Structural modulation of reactivity/activity in design of improved benzothiophene selective estrogen receptor modulators: induction of chemopreventive mechanisms

Dietz²,

Dunlap

et al. 2007

Molecular Cancer Therapeutics

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The benzothiophene selective estrogen receptor modulators (SERM) raloxifene and arzoxifene are in clinical use and clinical trials for chemoprevention of breast cancer and other indications. These SERMs are ''oxidatively labile'' and therefore have potential to activate antioxidant responsive element (ARE) transcription of genes for cytoprotective phase II enzymes such as NAD(P)Hdependent quinone oxidoreductase 1 (NQO1). To study this possible mechanism of cancer chemoprevention, a family of benzothiophene SERMs was developed with modulated redox activity, including arzoxifene and its metabolite desmethylarzoxifene (DMA). The relative antioxidant activity of these SERMs was assayed and correlated with induction of NQO1 in murine and human liver cells. DMA was found to induce NQO1 and to activate ARE more strongly than other SERMs, including raloxifene and 4-hydroxytamoxifen. Livers from female, juvenile rats treated for 3 days with estradiol and/or with the benzothiophene SERMs arzoxifene, DMA, and F-DMA showed substantial induction of NQO1 by the benzothiophene SERMs. No persuasive evidence in this assay or in MCF-7 breast cancer cells was obtained of a major role for the estrogen receptor in induction of NQO1 by the benzothiophene SERMs. These results suggest that arzoxifene might provide chemopreventive benefits over raloxifene and other SERMs via metabolism to DMA and stimulation of ARE-mediated induction of phase II enzymes. The correlation of SERM structure with antioxidant activity and NQO1 induction also suggests that oxidative bioactivation of SERMs may be modulated to enhance chemopreventive activity. [Mol Cancer Ther 2007;6(9):2418 -28]

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Differential responses from seven mammalian cell lines to the treatments of detoxifying enzyme inducers

Cited by 85 publications

References 22 publications

Molecular Targets of Dietary Phenethyl Isothiocyanate and Sulforaphane for Cancer Chemoprevention

Molecular Targets of Dietary Phenethyl Isothiocyanate and Sulforaphane for Cancer Chemoprevention

Chemoprotection by sulforaphane: Keep one eye beyond Keap1

Structural modulation of reactivity/activity in design of improved benzothiophene selective estrogen receptor modulators: induction of chemopreventive mechanisms

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