Sulforaphane and related mustard oils in focus of cancer prevention and therapy

Herr, Ingrid; Lozanovski, Vladimir J; Houben, Philipp; Schemmer, Peter; Büchler, Markus W.

doi:10.1007/s10354-012-0163-3

Cited by 27 publications

(22 citation statements)

References 59 publications

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“…Our recent results demonstrate that sulforaphane sensitizes resistant pancreatic CSCs to TRAIL-induced apoptosis through the inhibition of basal and TRAIL-induced NF-κB activity (9). Based on several promising animal and epidemiological studies, prospective clinical trials with sulforaphane-enriched broccoli sprout extracts are ongoing in the US to examine the effects on atypical nevi and bladder and prostate cancer (10). A pilot study at our clinic has been initiated to evaluate the effects of sulforaphane-enriched broccoli sprouts on patients with advanced pancreatic cancer.…”

Section: Introductionmentioning

confidence: 99%

Sulforaphane and TRAIL induce a synergistic elimination of advanced prostate cancer stem-like cells

Labsch

Liu

Bauer

et al. 2014

International Journal of Oncology

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Advanced androgen-independent prostate cancer (AIPC) is an aggressive malignancy with a poor prognosis. Apoptosis-resistant cancer stem cells (CSCs) have been identified in AIPC and are not eliminated by current therapeutics. Novel therapeutic options, which are currently being evaluated in patient studies, include TRAIL and the broccoli-derived isothiocyanate sulforaphane. Although neither agent targets normal cells, TRAIL induces apoptosis in most cancer cells, and sulforaphane eliminates CSCs. In this study, the established AIPC cell lines DU145 and PC3, with enriched CSC features, and primary patient-derived prostate CSCs were treated with sulforaphane and recombinant soluble TRAIL. We examined the effects of these drugs on NF-κB activity, self-renewal and differentiation potential, and stem cell signaling via spheroid- and colony-forming assays, FACS and western blot analyses, immunohistochemistry, and an antibody protein array in vitro and after xenotransplantation. We largely found a stronger effect of sulforaphane on CSC properties compared to TRAIL, though the agents acted synergistically when applied in combination. This was associated with the inhibition of TRAIL-induced NF-κB binding; CXCR4, Jagged1, Notch 1, SOX 2, and Nanog expression; ALDH1 activity inhibition; and the elimination of differentiation and self-renewal potential. In vivo, tumor engraftment and tumor growth were strongly inhibited, without the induction of liver necrosis or other obvious side effects. These findings suggest that sulforaphane shifts the balance from TRAIL-induced survival signals to apoptosis and thus explains the observed synergistic effect. A nutritional strategy for high sulforaphane intake may target the cancer-specific activity of TRAIL in CSCs.

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Section: Introductionmentioning

confidence: 99%

Sulforaphane and TRAIL induce a synergistic elimination of advanced prostate cancer stem-like cells

Labsch

Liu

Bauer

et al. 2014

International Journal of Oncology

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“…Vegetables of the cruciferous family such as broccoli seem to play a special role [17]. Crucifers produce mustard oils to protect themselves from pests.…”

Section: Ingrid Herrmentioning

confidence: 99%

Proceedings of the 5th annual symposium of the German Society for Paleo Nutrition held in 2017

Steger¹

2017

jevohealth

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“…Our recent results demonstrated that sulforaphane sensitizes pancreatic CSCs to chemotherapy by inhibiting their self-renewal potential, apoptosis resistance and NF-κB activity [8-11]. Based on several promising animal and epidemiological studies, prospective clinical trials with sulforaphane-enriched broccoli sprout extracts are ongoing in the U.S. to examine the effect on atypical nevi, bladder and prostate cancer [12], and a pilot study recently began at our clinic to evaluate the effect of this nutritional strategy on patients with advanced PDA.…”

Section: Introductionmentioning

confidence: 99%

Sulforaphane counteracts aggressiveness of pancreatic cancer driven by dysregulated Cx43-mediated gap junctional intercellular communication

Förster

Rausch

Zhang³

et al. 2014

Oncotarget

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The extreme aggressiveness of pancreatic ductal adenocarcinoma (PDA) has been associated with blocked gap junctional intercellular communication (GJIC) and the presence of cancer stem cells (CSCs). We examined whether disturbed GJIC is responsible for a CSC phenotype in established and primary cancer cells and patient tissue of PDA using interdisciplinary methods based in physiology, cell and molecular biology, histology and epigenetics. Flux of fluorescent dyes and gemcitabine through gap junctions (GJs) was intact in less aggressive cells but not in highly malignant cells with morphological dysfunctional GJs. Among several connexins, only Cx43 was expressed on the cell surface of less aggressive and GJIC-competent cells, whereas Cx43 surface expression was absent in highly malignant, E-cadherin-negative and GJIC-incompetent cells. The levels of total Cx43 protein and Cx43 phosphorylated at Ser368 and Ser279/282 were high in normal tissue but low to absent in malignant tissue. si-RNA-mediated inhibition of Cx43 expression in GJIC-competent cells prevented GJIC and induced colony formation and the expression of stem cell-related factors. The bioactive substance sulforaphane enhanced Cx43 and E-cadherin levels, inhibited the CSC markers c-Met and CD133, improved the functional morphology of GJs and enhanced GJIC. Sulforaphane altered the phosphorylation of several kinases and their substrates and inhibition of GSK3, JNK and PKC prevented sulforaphane-induced CX43 expression. The sulforaphane-mediated expression of Cx43 was not correlated with enhanced Cx43 RNA expression, acetylated histone binding and Cx43 promoter de-methylation, suggesting that posttranslational phosphorylation is the dominant regulatory mechanism. Together, the absence of Cx43 prevents GJIC and enhances aggressiveness, whereas sulforaphane counteracts this process, and our findings highlight dietary co-treatment as a viable treatment option for PDA.

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Sulforaphane and related mustard oils in focus of cancer prevention and therapy

Cited by 27 publications

References 59 publications

Sulforaphane and TRAIL induce a synergistic elimination of advanced prostate cancer stem-like cells

Sulforaphane and TRAIL induce a synergistic elimination of advanced prostate cancer stem-like cells

Proceedings of the 5th annual symposium of the German Society for Paleo Nutrition held in 2017

Sulforaphane counteracts aggressiveness of pancreatic cancer driven by dysregulated Cx43-mediated gap junctional intercellular communication

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