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. 2013 Dec;52(8):1949-58.
doi: 10.1007/s00394-013-0499-5. Epub 2013 Feb 7.

Sulforaphane Inhibits Growth of Phenotypically Different Breast Cancer Cells

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Free PMC article

Sulforaphane Inhibits Growth of Phenotypically Different Breast Cancer Cells

Anna Pawlik et al. Eur J Nutr. .
Free PMC article

Erratum in

  • Eur J Nutr. 2013 Dec;52(8):1959

Abstract

Purpose: Cancer development and resistance to chemotherapy correlates with aberrant activity of mitogenic pathways. In breast cancers, pro-survival PI3K-Akt-mTOR-S6K1 [corrected] 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-PI3K-Akt-mTOR-S6K1[corrected] signaling pathway to this compound.

Methods: 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.

Results: 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.

Conclusion: These results indicate that SFN is a potent inhibitor of the viability of breast cancer cells representing different activity of the ErbB2/ER-PI3K-Akt-mTOR-S6K1 [corrected] pro-survival pathway and suggest that it targets downstream elements of the pathway.

Figures

Fig. 1
Fig. 1
Sulforaphane decreases viability of phenotypically different cells in a dose-dependent manner. MDA MB 231, MCF-7, MDA MB 468 and SKBR-3 cells were treated with DMSO (0) or different concentrations of SFN (5, 10, 20, 30 or 40 μM) for 24 h. Their viability was assayed by MTT method as described in “Materials and methods”. Each point is mean (±SE) of three experiments done in triplicate
Fig. 2
Fig. 2
Ultrastructure of breast cancer cells in transmission electron microscopy treated or not with 40 μM SFN for 6 h. Arrows indicate autophagosomal vacuoles. Magnification ×1,650
Fig. 3
Fig. 3
Autophagy induction by SFN in breast cancer cells revealed as punctuate localization of GFP-LC3, marker of autophagy. Cells were treated with DMSO (control) or 40 μM SFN for 6 h. Magnification ×1,000 (left panel in control and SFN group); on the right panel, enlarged respective cell is shown
Fig. 4
Fig. 4
SFN decreases phosphorylation level of Akt and S6K1 kinases in all studied cell lines. Immunoblotting for p-S6K1 (Thr389) and p-Akt (Ser473) using lysates from MDA MB 231, MCF-7, MDA MB 468 and SKBR-3 cells treated with different concentrations of SFN for 3 h. The blots were stripped and reprobed with anti-β-actin antibody to ensure equal protein loading
Fig. 5
Fig. 5
SFN inhibits protein synthesis in human breast cancer cells. MDA MB 231, MCF-7, MDA MB 468 were treated with various concentrations of SFN for 3 h in the presence of a protein precursor, [3H] –leucine. Cells were harvested, and radioactivity of TCA-precipitable material was estimated as described in “Materials and methods”. Results shown are mean ± SE of two independent experiments performed in duplicate (MDA MB 231 and MCF-7) or in triplicate (MDA MB 468), *significantly different (P < 0.01) compared with DMSO-treated control by one-way ANOVA followed by Dunnett’s multiple comparison test

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