Home
 
SULFORAPHANE



RESEARCH


Sulforaphane inhibits growth of phenotypically different breast cancer cells.
Source:
Pawlik A, Wiczk A, Kaczyńska A, Antosiewicz J, Herman-Antosiewicz A. Eur J Nutr. 2013 Feb 7.
Cancer development and resistance to chemotherapy correlates with aberrant activity of mitogenic pathways. In breast cancers, pro-survival PI3K-AktmTOR-S6K1 signaling pathway is often hyperactive due to overexpression of genes coding for growth factors or estrogen receptors, constitutive activation of PI3K or Akt and loss of PTEN, a negative regulator of the pathway. Since epidemiologic as well as rodent tumor studies indicate that sulforaphane (SFN), a constituent of many edible cruciferous vegetables, might be a potent inhibitor of mammary carcinogenesis, we analyzed the response of four breast cancer cell lines representing different abnormalities in ErbB2/ER-PI3KAktmTOR- S6K1 signaling pathway to this compound.
Four different breast cancer cell lines were used: MDA MB 231, MCF-7, SKBR-3 and MDA MB 468. Cell viability and ultrastructure, protein synthesis, autophagy induction and phosphorylation status of Akt and S6K1 kinases upon SFN treatment were determined. We observed that all four cell lines are similarly sensitive to SFN. SFN decreased phosphorylation of Akt and S6K1 kinases and at higher concentrations induced autophagy in all studied cell lines. Moreover, global protein synthesis was inhibited by SFN in investigated cell lines in a dose-dependent manner.
These results indicate that SFN is a potent inhibitor of the viability of breast cancer cells representing different activity of the ErbB2/ER-PI3K-AktmTOR-S6K1 pro-survival pathway and suggest that it targets downstream elements of the pathway.

Sulforaphane suppresses TNF-α-mediated activation of NF-κB and induces apoptosis through activation of reactive oxygen species-dependent caspase-3
Moon D-O, Kim M-O, Kang S-H, et al. Cancer Letters. Volume 274, Issue 1, 8 February 2009, Pages 132–142 http://dx.doi.org/10.1016/j.canlet.2008.09.013, Sulforaphane (SFN) is a biologically active compound extracted from cruciferous vegetables, and possessing potent anti-cancer and anti-inflammatory activities. Here, we show that tumor necrosis factor-α (TNF-α), in combination with a sub-toxic dose of SFN, significantly triggered apoptosis in TNF-α-resistant leukemia cells (THP-1, HL60, U937, and K562), which was associated with caspase activity and poly (ADP-ribose)-polymerase cleavage. We also report that SFN non-specifically inhibited TNF-α-induced NF-κB activation through the inhibition of IκBα phosphorylation, IκBα degradation, and p65 nuclear translocation. This inhibition correlated with the suppression of NF-κB-dependent genes involved in anti-apoptosis (IAP-1, IAP-2, XIAP, Bcl-2, and Bcl-xL), cell proliferation (c-Myc, COX-2, and cyclin D1), and metastasis (VEGF and MMP-9). These effects suggest that SFN inhibits TNF-α-induced NF-κB activation through the suppression of IκBα degradation, leading to reduced expression of NF-κB-regulated gene products. Combined treatment with SFN and TNF-α was also accompanied by the generation of reactive oxygen species (ROS). Pre-treatment with N-acetyl-l-cysteine significantly attenuated the combined treatment-induced ROS generation and caspase-3-dependent apoptosis, implying the involvement of ROS in this type of cell death. In conclusion, the results of the present study indicate that SFN suppresses TNF-α-induced NF-κB activity and induces apoptosis through activation of ROS-dependent caspase-3.

Dual roles of sulforaphane in cancer treatment.
Xu T, Ren D, Sun X, Yang G. Anticancer Agents Med Chem. 2012 Nov;12(9):1132-42.
Sulforaphane (SFN), one of naturally occurring isothiocyanates (ITCs), has huge cancer chemopreventive potential. It modulates cell death, cell cycle, angiogenesis, susceptibility to carcinogens, invasion and metastasis and possesses antioxidant activities. It functions as an inhibitor of phase I enzymes and also as an inducer of phase II detoxification enzymes through different ways. NF-E2- related factor-2(Nrf-2), as well as mitogen-activated protein kinase (MAPK), is regulated by SFN.
Intriguingly, strong evidence has showed the dark side of Nrf-2: stable upregulation of Nrf-2-mediated survival pathway would protect cancer cells from a subset of chemotherapeutic agents tested. This suggested that overexpression of Nrf-2 resulted in enhanced resistance of cancer cells to chemotherapeutic agents. Hence, future studies will focus on clarifying the exact time and dose of SFN to modulate the Nrf-2 signal pathway during chemotherapy and the efficacy of coadministration of Nrf-2 modulators during chemotherapy in order to make full use of the beneficial effect of this agent while eliminating the potential side effects.






 
CopyRight 2012 - ICOP