| Properties | Information | |
|---|---|---|
| PhytoCAT-ID | PhytoCAT-1482 | |
| Phytochemical name or plant extracts | Sulforaphane | |
| PMID | 20944112 | |
| Literature evidence | Treatment with autophagy inhibitor bafilomycin A1 (but not 3-methyladenine) with SFN significantly enhanced apoptosis, which was accompanied by increases in the level of BAX and the cleavage of caspase-3 and poly(ADP-ribose)polymerase (PARP)-1 and decreases in the mitochondrial membrane potential (??m). | |
| IUPAC name | 1-isothiocyanato-4-methylsulfinylbutane | |
| Phytochemicals’ class or type of plant extracts | Isothiocyanate | |
| Source of phytochemicals or plant Extracts | Cruciferous vegetables | |
| Geographical availability | France, Great Britain, Spain | |
| Plant parts | NA | |
| Other cancers | Breast cancer, Colon cancer, Prostate cancer | |
| Target gene or protein | MMP7, MMP14, p38, Caspase 7, Bax, EMT, CR1, CRIPTO-3/TDGF1P3 (CR3, a homologue of CR1), Nanog, ALDH1A1, Wnt3, Notch4, KLF4, hTERT, CDKN2A, PTEN, RARbeta2, DNMT1, p53, p21, PBR, vimentin, Twist1, POU5F1, IL-1beta, IL-6, TNF-alpha, IFN-gamma,IL-4, PDGF, VEGF. | |
| Gene or Protein evidence | TPA-induced MMP-9 expression and cell invasion were decreased by sulforaphane treatment. Sulforaphane upregulates p38 in MCF-7 cells and prevented TPA-reduced phosphorylation of p38 in M13SV1 cells, but activated caspase-7 associated with apoptosis in MCF-7 cells. SFN significantly enhanced apoptosis, which was accompanied by increases in the level of BAX. The results of the current study suggests that CIS when supplemented with SFN, inhibits metastasis and stemness potential of TNBC cells by down regulating SIRTs-mediated EMT cascade. Further analysis of gene expression in these TNBC tumor cells revealed that sulforaphane significantly decreases the expression of cancer-specific CR1, CRIPTO-3/TDGF1P3 (CR3, a homologue of CR1), and various stem cell markers including Nanog, aldehyde dehydrogenase 1A1 (ALDH1A1), Wnt3, and Notch4. The combination of GEN and SFN is also effective in downregulating hTERT levels, which is known to be activated when KLF4 binds to its promoter region. Inhibition of breast cancer cell growth by the combination of clofarabine and sulforaphane involves epigenetically mediated CDKN2A upregulation In both MCF-7 and MDA-MB-231 cells, SFN at IC 50 (22 and 46 μ M , respectively) and a physiologically relevant 10 μ M concentration lead to hypomethylation of PTEN and RARbeta2 promoters with concomitant gene upregulation. In the present study, we investigated the effects of sulforaphane (SFN), a phytochemical from cruciferous vegetables, on the methylation and expression of PTEN and RARbeta2 tumour suppressor genes as well as on the expression of regulators of DNA methylation reaction, DNMT1 , p53 , and p21 , in MCF-7 and MDA-MB-231 human breast cancer cells with different invasive potential. SFN downregulated PBR and vimentin expression in a dose dependent manner, but significantly affected neither HIF-1alpha, nor CA IX protein expression, nor VEGF and GLUT1 mRNA levels. Among studied MMPs, MMP7 and MMP14 mRNA were downregulated while no apparent effect on MMP1, MMP3 and MMP9 was observed. Further, we found significant down regulation of Twist1 and POU5F1, transcription factors that mediate EMT and the self-renewal of undifferentiated embryonic stem cells. SFN reduced also the production of pro-inflammatory cytokines IL-1beta, IL-6, TNF-alpha, IFN-gamma, immunomodulating cytokine IL-4 and growth factors involved in angiogenesis PDGF and VEGF. | |
| Target pathways | NF-kB pathway Akt-mTOR-S6K1 pathway | |
| IC50 | 13.7 +/- 0.82 µM against MCF-7/wt 40.5 +/- 1.25 µM against MCF-12A | |
| Potency | These results indicate a cytoprotective role of autophagy against SFN-induced apoptosis and that the combination of SFN treatment with autophagy inhibition may be a promising strategy for breast cancer control. | |
| Cell line/ mice model | MCF-7, MDA-MB-231, SKBR-3, MCF-12A, HeLa | |
| Additional information | Sulforaphane reduced proliferation in MCF-7 cells and inhibited cyclooxygenase-2 expression in M13SV1 cells treated with 12-O-tetradecanoylphorbol-13-acetate (TPA). Treatment with autophagy inhibitor bafilomycin A1 (but not 3-methyladenine) with SFN significantly enhanced apoptosis, which was accompanied by increases in the level of BAX and the cleavage of caspase-3 and poly(ADP-ribose)polymerase (PARP)-1 and decreases in the mitochondrial membrane potential (??m). Thus, the use of sulforaphane for chemoprevention of TNBC is plausible and warrants further clinical evaluation. Our results suggest that sulforaphane may control the malignant proliferation of CSCs in TNBC via Cripto-mediated pathway by either suppressing its expression and/or by inhibiting Cripto/Alk4 protein complex formation. | |
| PubChem ID | 5350 | |
| Additional PMIDs | 27281367 31739165 32891712 33456268 26372775 28534825 32111265 15337839 19712481 20625516 21295962 24002734 26511489 29040973 29899271 30679159 32471217 18602823 29104175 29305271 15333709 15501721 18090122 18952594 19728765 20944112 23615261 28599444 29518137 33640782 21595016 31670945 21992498 26014809 26134366 28334682 29764806 24191056 28912888 29634384 29725861 31456191 32184225 30641176 19144873 19197985 23752191 25725373 27478970 29689276 31846091 22662208 28839265 29731172 19940992 24950293 30524952 31618725 31454641 32679526 | |
| Additional sources of information | https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:279435-1 | |
| Safety | NA |