Forkhead Box Q1 Is a Novel Target of Breast Cancer Stem Cell Inhibition by Diallyl Trisulfide

Kim, Su‐Hyeong; Kaschula, Catherine H.; Priedigkeit, Nolan; Lee, Adrian V.; Singh, Shivendra V.

doi:10.1074/jbc.m116.715219

Cited by 64 publications

(125 citation statements)

References 49 publications

(67 reference statements)

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“…We have drawn attention to studies indicating that the mechanism of therapeutic action of garlic-derived compounds is connected with their influence on ALDH activity. Kim et al indicated that the inhibition of ALDH activity was one of the mechanisms by which DATS suppressed the growth of breast cancer cells in vitro and in vivo [44]. It was observed that ALDH activity in the liver cells was reduced in mice intragastrically administered fresh garlic juice for eight days [45].…”

Section: Discussionmentioning

confidence: 99%

The Effects of Different Garlic-Derived Allyl Sulfides on Anaerobic Sulfur Metabolism in the Mouse Kidney

Iciek¹,

Bilska‐Wilkosz²,

Górny³

et al. 2016

Antioxidants

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Diallyl sulfide (DAS), diallyl disulfide (DADS) and diallyl trisulfide (DATS) are major oil-soluble organosulfur compounds of garlic responsible for most of its pharmacological effects. The present study investigated the influence of repeated intraperitoneally (ip) administration of DAS, DADS and DATS on the total level of sulfane sulfur, bound sulfur (S-sulfhydration) and hydrogen sulfide (H2S) and on the activity of enzymes, which catalyze sulfane sulfur formation and transfer from a donor to an acceptor in the normal mouse kidney, i.e., γ-cystathionase (CSE) and rhodanese (TST). The activity of aldehyde dehydrogenase (ALDH), which is a redox-sensitive protein, containing an –SH group in its catalytic center, was also determined. The obtained results indicated that all tested compounds significantly increased the activity of TST. Moreover, DADS and DATS increased the total sulfane sulfur level and CSE activity in the normal mouse kidney. ALDH activity was inhibited in the kidney after DATS administration. The results indicated also that none of the studied allyl sulfides affected the level of bound sulfur or H2S. Thus, it can be concluded that garlic-derived DADS and DATS can be a source of sulfane sulfur for renal cells but they are not connected with persulfide formation.

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Section: Discussionmentioning

confidence: 99%

The Effects of Different Garlic-Derived Allyl Sulfides on Anaerobic Sulfur Metabolism in the Mouse Kidney

Iciek¹,

Bilska‐Wilkosz²,

Górny³

et al. 2016

Antioxidants

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“…Inhibition of the H3 K27me3 demethylases KDM6 A/B by GSKÀJ4 was shown to promote EMT in MCF-7 and HMLER cells, [74] suggesting that targeting epigenetic modifiers could provide the means to alter EMT for therapeutic purposes. Diallyl trisulfide (DAST) targets FOXQ1, [75] a protein implicated in embryonic development, cell cycle regulation, tissue-specific gene expression, cell signaling, and tumorigenesis in MCF-7 and SUM159 cells. It was shown that FOXQ1 is over-expressed in the CSCs, implying that this transcription factor may represent a suitable therapeutic target.…”

Section: Miscellaneousmentioning

confidence: 99%

Targeting Cancer Stem Cells with Small Molecules

Müller

Cañeque

Acevedo

et al. 2017

Israel Journal of Chemistry

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Cancers arise as a result of physiological imbalances and subsequent uncontrolled cell division. Cancer initiation requires a set of biochemical alterations, including some occurring at the genetic and epigenetic levels. Thus, tumors are heterogeneous in nature making it challenging to selectively target different cancer cells by means of small molecule intervention. The paradigm of cancer stem cells (CSCs) describes subpopulations of cells with high selfrenewal and tumor-seeding capacity. These cells, typically refractory to conventional therapies, can give rise to relapse after treatment. Combinatorial strategies, including drugs that selectively target this population of cells, have emerged in recent years. Here, we review how discovery-basedunbiased -screening approaches [1] have helped identify small molecules that specifically target CSCs. We also highlight biological pathways characteristic of CSCs that can potentially be selectively targeted in a hypothesis-driven manner by small molecules. We describe molecules that effectively target CSCs and emphasize what is known about their biological modes of action. The diversity and complexity of biochemical processes that CSCs may be addicted to, raises the question of how selective targeting of these pathways can be achieved. This challenge may be addressed by the continuing production of structurally complex and diverse small molecules using target and diversity-oriented synthesis approaches.[2]

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“…DACH1 expression is lost in invasive BC . FoxQ1 is highly expressed in triple‐negative BC, displays an inverse correlation with the levels of DACH1 and localizes to DACH1 promoter in BC cells . The DATS treatment led to decrease of FoxQ1 protein levels along with inhibiting BC progression and causing a decline in BC stem cell population .…”

Section: Determinants Of Bc Risk: Considerations For Bc Prevention Anmentioning

confidence: 99%

Translational opportunities for broad‐spectrum natural phytochemicals and targeted agent combinations in breast cancer

Nagaprashantha

Adhikari

Singhal

et al. 2017

Intl Journal of Cancer

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Breast cancer (BC) prevention and therapy in the context of life-style risk factors and biological drivers is a major focus of developmental therapeutics in oncology. Obesity, alcohol, chronic estrogen signaling and smoking have distinct BC precipitating and facilitating effects that may act alone or in combination. A spectrum of signaling events including enhanced oxidative stress and changes in estrogen-receptor (ER)-dependent and -independent signaling drive the progression of BC. Breast tumors modulate ERα/ERβ ratio, upregulate proliferative pathways driven by ERα and HER2 with a parallel loss and/or downregulation of tumor suppressors such as TP53 and PTEN which together impact the efficacy of therapeutic strategies and frequently lead to emergence of drug resistance. Natural phytochemicals modulate oxidative stress, leptin, integrin, HER2, MAPK, ERK, Wnt/β-catenin and NFκB signaling along with regulating ERα and ERβ, thereby presenting unique opportunities for both primary and combinatorial interventions in BC. In this regard, this article focuses on critical analyses of the evidence from multiple studies on the efficacy of natural phytochemicals in BC. In addition, areas in which the combinations of such effective natural phytochemicals with approved and/or developing anticancer agents can be translationally beneficial are discussed to derive evidence-based inference for addressing challenges in BC control and therapy.

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Forkhead Box Q1 Is a Novel Target of Breast Cancer Stem Cell Inhibition by Diallyl Trisulfide

Cited by 64 publications

References 49 publications

The Effects of Different Garlic-Derived Allyl Sulfides on Anaerobic Sulfur Metabolism in the Mouse Kidney

The Effects of Different Garlic-Derived Allyl Sulfides on Anaerobic Sulfur Metabolism in the Mouse Kidney

Targeting Cancer Stem Cells with Small Molecules

Translational opportunities for broad‐spectrum natural phytochemicals and targeted agent combinations in breast cancer

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