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Suppression of 12-O-Tetradecanoylphorbol-13-Acetate-Induced MCF-7 Breast Adenocarcinoma Cells Invasion/Migration by α-Tomatine Through Activating PKCα/ERK/NF-κB-Dependent MMP-2/MMP-9 Expressions

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Abstract

α-Tomatine, isolated from Lycopersicon esculentum Linn., is a naturally occurring glycoalkaloids in immature green tomatoes. Some reports demonstrated that α-tomatine had various anti-carcinogenic properties. First, the result demonstrated α-tomatine could inhibit TPA-induced the abilities of the adhesion, morphology/actin cytoskeleton arrangement, invasion, and migration by cell–matrix adhesion assay, immunofluorescence stain assay, Boyden chamber invasion assay, and wound-healing assay. Data also showed α-tomatine could inhibit the activation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and protein kinase C-α (PKCα) involved in the downregulation of the enzyme activities and messenger RNA levels of matrix metalloproteinase-2/9 (MMP-2/MMP-9) induced by TPA. Next, α-tomatine also strongly inhibited TPA-induced the activation of nuclear factor kappa B (NF-κB) and phospho-inhibitor of kappa Bα (phospho-IκBα). In addition, TPA-induced translocation of PKC-α from cytosol to membranes, and suppression of TPA elicited the expression of PKC-α by adding the PKC-α inhibitors, GF-109203X and Gö-6983. The treatment of specific inhibitor for ERK (U0126) to MCF-7 cells could inhibit TPA-induced MMP-2/MMP-9 and phospho-ERK along with an inhibition on cell invasion and migration. Application of α-tomatine to prevent the invasion/migration of MCF-7 cells through blocking PKCα/ERK/NF-κB activation is first demonstrated herein.

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Abbreviations

TPA:

12-O-Tetradecanoylphorbol-13-acetate

MMPs:

Matrix metalloproteinases

ECM:

Extracellular matrix

PKCα:

Protein kinase C-α

ERK:

Extracellular signaling-regulating kinase

JNK/SAPK:

c-Jun N-terminal kinase/stress-activated protein kinase

p38 MAPK:

p38 Mitogen-activated protein kinase

PI3KAkt:

Phosphoinositide 3-kinase/protein kinase B

NF-κB:

Nuclear factor kappa B

IκBα:

Inhibitor of NF-κB

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Acknowledgments

This work was supported by the grant from the Research Program of Yongkang Veterans Hospital, Tainan, Taiwan (VHYK-9902).

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Authors and Affiliations

  1. Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Kaohsiung, 807, Taiwan

    Min-Der Shi & Li-Yu Tsai

  2. Department of Medical Technology, Kaohsiung Veterans General Hospital Tainan Branch, Tainan, 710, Taiwan

    Min-Der Shi

  3. Department of Medical Laboratory Science and Biotechnology, Chung Hwa University of Medical Technology, Tainan, 717, Taiwan

    Min-Der Shi

  4. Department of Biological Science and Technology and Graduate Institute of Biomedical Science, Chung Hwa University of Medical Technology, No. 89, Wen-Hwa 1st Street, Jen-Te, Tainan, 717, Taiwan

    Yuan-Wei Shih, Ya-Shan Lee & Yueh-Feng Cheng

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Correspondence to Yuan-Wei Shih or Li-Yu Tsai.

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Shi, MD., Shih, YW., Lee, YS. et al. Suppression of 12-O-Tetradecanoylphorbol-13-Acetate-Induced MCF-7 Breast Adenocarcinoma Cells Invasion/Migration by α-Tomatine Through Activating PKCα/ERK/NF-κB-Dependent MMP-2/MMP-9 Expressions. Cell Biochem Biophys 66, 161–174 (2013). https://doi.org/10.1007/s12013-012-9465-8

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