Sulforaphane prevents mouse skin tumorigenesis during the stage of promotion. Cancer Lett
Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, IL 60612, USA.Cancer Letters (Impact Factor: 5.62). 06/2006; 236(1):72-9. DOI: 10.1016/j.canlet.2005.05.007
Sulforaphane (SF), a natural product from broccoli, is known to enhance detoxification of carcinogens and block initiation of chemically-induced carcinogenesis in animal models. Cell culture and xenograft studies suggest additional roles for SF, inhibiting growth of tumors, arresting the cell cycle and enhancing apoptosis. As currently reported, topical SF (1, 5 or 10 micromol/mouse) significantly inhibited 7,12-dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol 13-acetate (TPA)-induced mouse skin tumorigenesis, using either an anti-promotion protocol (SF from 1 week after carcinogen until the end of the study) or a combined anti-initiation, anti-promotion protocol (SF 7 days prior to carcinogen until the end of the study). Surprisingly, no significant effect was observed in an anti-initiation protocol (SF from 7 days prior to 7 days after carcinogen). Separately, SF inhibited TPA-induced ornithine decarboxylase activity in mouse skin, an obligate step in TPA-induced promotion of carcinogenesis. These data link this molecular mechanism to SF-dependent inhibition of the promotion of tumorigenesis.
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- "However, a very efficient tumor-suppressive effect of sulforaphane was observed when the application was started one week after DMBA treatment and continued until the end of the tumor observation. This finding suggests that sulforaphane is required during the stage of tumor promotion . The efficacy of sulforaphane for cancer prevention was confirmed in in vitro studies with cultured JB6 keratinocytes, where sulforaphane inhibited TPA-induced cellular transformation, which was abrogated on Nrf2 knockdown. "
ABSTRACT: The skin is frequently exposed to environmental challenges, such as UV irradiation, toxic chemicals or mechanical wounding. These insults cause an increase in the levels of reactive oxygen species, resulting in oxidative stress and concomitant inflammation, skin aging and even cancer development. Therefore, an efficient antioxidant defense strategy is of major importance in this tissue. Since the NRF2 transcription factor regulates a battery of genes involved in the defense against reactive oxygen species and in compound metabolism, it plays a key role in skin homeostasis, repair and disease. In this review we summarize current knowledge on the expression and function of NRF2 in normal skin, its role in the acute and chronic UV response as well as in the pathogenesis of epithelial skin cancer and of different inflammatory skin diseases. Finally, we discuss the potential of NRF2-activating compounds for skin protection under stress conditions and for the treatment of major human skin disorders. Copyright © 2015. Published by Elsevier Inc.Free Radical Biology and Medicine 04/2015; DOI:10.1016/j.freeradbiomed.2015.04.018 · 5.74 Impact Factor
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- "Chemical proteomics aimed at characterizing the effects of drug candidates could sometimes lead to the discovery of new drug targets. For example, sulforaphane (SFN) is known to have antimicrobial and anticancer properties in experimental models.110–112 SFN can modulate multiple cellular targets involved in cancer development including DNA protection, inhibition of cancer cell proliferation, induction of apoptosis, inhibition of neoangiogenesis, progression of benign tumors to malignant tumors, and metastasis.112,113 "
ABSTRACT: Proteomic approaches are continuing to make headways in cancer research by helping to elucidate complex signaling networks that underlie tumorigenesis and disease progression. This review describes recent advances made in the proteomic discovery of drug targets for therapeutic development. A variety of technical and methodological advances are overviewed with a critical assessment of challenges and potentials. A number of potential drug targets, such as baculoviral inhibitor of apoptosis protein repeat-containing protein 6, macrophage inhibitory cytokine 1, phosphoglycerate mutase 1, prohibitin 1, fascin, and pyruvate kinase isozyme 2 were identified in the proteomic analysis of drug-resistant cancer cells, drug action, and differential disease state tissues. Future directions for proteomics-based target identification and validation to be more translation efficient are also discussed.Drug Design, Development and Therapy 10/2013; 7:1259-1271. DOI:10.2147/DDDT.S52216 · 3.03 Impact Factor
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- "An important group of agents that have this property are the organosulfur compounds such as isothiocyanates (ITCs), abundant in cruciferous vegetables for which consumption has epidemiologically shown an inverse link with pancreatic cancer. ITCs have been shown to exhibit several potential chemoprotective activities in cell and animal models , , , . We have previously shown that oral administration of sulforaphane inhibited the growth of PC-3 cells orthotopically implanted in the prostate of nude mice by inducing apoptosis and inhibiting tumor cell proliferation, metastasis and angiogenesis . "
ABSTRACT: Dysregulation of the sonic hedgehog (Shh) signaling pathway has been associated with cancer stem cells (CSC) and implicated in the initiation of pancreatic cancer. Pancreatic CSCs are rare tumor cells characterized by their ability to self-renew, and are responsible for tumor recurrence accompanied by resistance to current therapies. The lethality of these incurable, aggressive and invasive pancreatic tumors remains a daunting clinical challenge. Thus, the objective of this study was to investigate the role of Shh pathway in pancreatic cancer and to examine the molecular mechanisms by which sulforaphane (SFN), an active compound in cruciferous vegetables, inhibits self-renewal capacity of human pancreatic CSCs. Interestingly, we demonstrate here that Shh pathway is highly activated in pancreatic CSCs and plays important role in maintaining stemness by regulating the expression of stemness genes. Given the requirement for Hedgehog in pancreatic cancer, we investigated whether hedgehog blockade by SFN could target the stem cell population in pancreatic cancer. In an in vitro model, human pancreatic CSCs derived spheres were significantly inhibited on treatment with SFN, suggesting the clonogenic depletion of the CSCs. Interestingly, SFN inhibited the components of Shh pathway and Gli transcriptional activity. Interference of Shh-Gli signaling significantly blocked SFN-induced inhibitory effects demonstrating the requirement of an active pathway for the growth of pancreatic CSCs. SFN also inhibited downstream targets of Gli transcription by suppressing the expression of pluripotency maintaining factors (Nanog and Oct-4) as well as PDGFRα and Cyclin D1. Furthermore, SFN induced apoptosis by inhibition of BCL-2 and activation of caspases. Our data reveal the essential role of Shh-Gli signaling in controlling the characteristics of pancreatic CSCs. We propose that pancreatic cancer preventative effects of SFN may result from inhibition of the Shh pathway. Thus Sulforaphane potentially represents an inexpensive, safe and effective alternative for the management of pancreatic cancer.PLoS ONE 09/2012; 7(9):e46083. DOI:10.1371/journal.pone.0046083 · 3.23 Impact Factor
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