| Properties | Information | |
|---|---|---|
| PhytoCAT-ID | PhytoCAT-1334 | |
| Phytochemical name or plant extracts | Benzyl isothiocyanate | |
| PMID | 17121941 | |
| Literature evidence | The BITC treatment caused rapid disruption of the mitochondrial membrane potential, leading to cytosolic release of apoptogenic molecules, which was accompanied by formation of autophagosome-like structures as revealed by transmission electron microscopy. | |
| IUPAC name | isothiocyanatomethylbenzene | |
| Phytochemicals’ class or type of plant extracts | Isothiocyanate | |
| Source of phytochemicals or plant Extracts | Cruciferous vegetables | |
| Geographical availability | NA | |
| Plant parts | NA | |
| Other cancers | Breast cancer, Colon cancer | |
| Target gene or protein | STAT-3, XIAP, Caspase 9, Caspase 3, Caspase 8, Bax, Bcl-2, Bcl-xL, Bak, sfRON, MFN2, MAPK, JNK, p38, E-cadherin, Vimentin, Fibronectin, Notch2, FocO1, PUMA, Ron, AKT | |
| Gene or Protein evidence | BITC can prevent the induction of STAT3 activation by Interleukin-6 in MDA-MB-453 breast cancer cells, BITC resulted in a marked decrease in protein level of XIAP as early as 8 hours after treatment. p53-Independent apoptosis by benzyl isothiocyanate in human breast cancer cells is mediated by suppression of XIAP expression. The BITC-mediated apoptosis was associated with generation of reactive oxygen species and cleavage of caspase-9, caspase-8, and caspase-3. The BITC-induced apoptosis correlated with induction of proapoptotic proteins Bax (MCF-7) and Bak (MDA-MB-231 and MCF-7) and down-regulation of antiapoptotic proteins Bcl-2 and Bcl-xL (MDA-MB-231). In conclusion, the present study provides novel mechanistic insights into the role of sfRON in apoptosis regulation by BITC and other electrophilic phytochemicals. Upon treatment with BITC, Bak dissociated from mitofusin 2 in both MCF-7 and MDA-MB-231 cells suggesting a crucial role for interaction of Bak and mitofusins in BITC-mediated inhibition of fusion and morphological dynamics. The BITC treatment caused activation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK), which function upstream of Bax activation in apoptotic response to various stimuli. Inhibition of MDA-MB-231 xenograft growth in vivo in female athymic mice by BITC administration was associated with an increase in protein level of E-cadherin and suppression of vimentin and fibronectin protein expression. In conclusion, the results of this study indicate that (a) BITC treatment activates Notch2 in cultured and xenografted human breast cancer cells, and (b) Notch2 activation impedes inhibitory effect of BITC on cell migration. In conclusion, the present study provides novel insights into the molecular circuitry of BITC-induced cell death involving FoxO1-mediated autophagy. Instead, the BITC-treated MCF-7 and MDA-MB-231 cells exhibited upregulation of p53 upregulated modulator of apoptosis (PUMA) protein. These results indicate increased glucose uptake/metabolism by BITC treatment in breast cancer cells suggesting that breast cancer chemoprevention by BITC may be augmented by pharmacological inhibition of AKT. The BITC treatment downregulated protein levels of Ron and sfRon in cultured breast cancer cells and in tumor xenografts. | |
| Target pathways | NA | |
| IC50 | For 1h, 2h, 3h, 6h, 48h: 17.0 ± 1.53 µM against MCF-7/wt 14.1 ± 1.46 µM against MCF-7/wt 10.3 ± 1.62 µM against MCF-7/wt 6.94 ± 0.46 µM against MCF-7/wt 4.11 ± 0.26 µM against MCF-7/wt | |
| Potency | NA | |
| Cell line/ mice model | MDA-MB-231, MCF-7, MCF-10A, MDA-MB-453, MDA-MB-361, Female athymic mice, SUM159, HCT-1, MCF-12A | |
| Additional information | Finally, KLF4 was recruited to the promoter of p21CIP1 as indicated by chromatin immunoprecipitation assay. These results indicate that induction of KLF4-p21CIP1 axis attenuates inhibitory effect of BITC on bCSC self-renewal. Translational implication of these findings is that breast cancer chemoprevention by BITC may be augmented with a combination regimen involving BITC and an inhibitor of KLF4. | |
| PubChem ID | 2346 | |
| Additional PMIDs | 25857724 27374852 18768478 19712481 21464039 22476855 22457718 22359675 15337839 17121941 23661606 30720225 20484174 30723175 | |
| Additional sources of information | NA | |
| Safety | In contrast, a normal human mammary epithelial cell line (MCF-10A) that was derived from fibrocystic breast disease, was resistant to BITC-mediated alterations in mitochondrial dynamics as well as apoptosis. |