A synthetic chalcone derivative, 2-hydroxy-3',5,5'-trimethoxychalcone (DK-139), suppresses the TNFα-induced invasive capability of MDA-MB-231 human breast cancer cells by inhibiting NF-κB-mediated GROα expression

Da Young Lee; Da Hyun Lee; Jung You Jung; Dongsoo Koh; Geum-Soog Kim; Young-Sup Ahn; Young Han Lee; Yoongho Lim; Soon Young Shin

doi:10.1016/j.bmcl.2015.10.094

A synthetic chalcone derivative, 2-hydroxy-3',5,5'-trimethoxychalcone (DK-139), suppresses the TNFα-induced invasive capability of MDA-MB-231 human breast cancer cells by inhibiting NF-κB-mediated GROα expression

Bioorg Med Chem Lett. 2016 Jan 1;26(1):203-8. doi: 10.1016/j.bmcl.2015.10.094. Epub 2015 Oct 30.

Authors

Da Young Lee¹, Da Hyun Lee², Jung You Jung³, Dongsoo Koh⁴, Geum-Soog Kim⁵, Young-Sup Ahn⁵, Young Han Lee⁶, Yoongho Lim⁷, Soon Young Shin⁸

Affiliations

¹ Division of Biological Sciences, Biology w/Spec Bioinformatics, Revelle College, University of California, San Diego, CA 92093, USA.
² Department of Biological Sciences, College of Biological Science and Biotechnology, Konkuk University, 120 Neundong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea.
³ Cancer and Metabolism Institute, Konkuk University, Seoul 143-701, Republic of Korea.
⁴ Department of Applied Chemistry, Dongduk Women's University, Seoul 136-714, Republic of Korea.
⁵ Department of Herbal Crop Research, National Institute of Horticultural and Herbal Science, Rural Development Administration, Eumseong 369-873, Republic of Korea.
⁶ Department of Biological Sciences, College of Biological Science and Biotechnology, Konkuk University, 120 Neundong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea; Cancer and Metabolism Institute, Konkuk University, Seoul 143-701, Republic of Korea.
⁷ Division of Bioscience and Biotechnology, BMIC, Konkuk University, Seoul 143-701, Republic of Korea.
⁸ Department of Biological Sciences, College of Biological Science and Biotechnology, Konkuk University, 120 Neundong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea; Cancer and Metabolism Institute, Konkuk University, Seoul 143-701, Republic of Korea. Electronic address: shinsy@konkuk.ac.kr.

PMID: 26602275
DOI: 10.1016/j.bmcl.2015.10.094

Abstract

2-Hydroxy-3',5,5'-trimenthoxyochalcone (DK-139) is a synthetic chalcone-derived compound. This study evaluated the biological activity of DK-139 on the inhibition of tumor metastasis. Growth-regulated oncogene-alpha (GROα) plays an important role in the progression of tumor development by stimulating angiogenesis and metastasis. In this study, DK-139 inhibited tumor necrosis factor alpha (TNFα)-induced GROα gene promoter activity by inhibiting of IκB kinase (IKK) in MDA-MB231 cells. In addition, DK-139 prevented the TNFα-induced cell migration, F-actin formation, and invasive capability of MDA-MB-231 cells. These findings suggest that DK-139 is a potential drug candidate for the inhibition of tumor cell locomotion and invasion via the suppression of NF-κB-mediated GROα expression.

Keywords: 2-Hydroxy-3′,5,5′-trimenthoxyochalcone; Growth-regulated oncogene-alpha; Human breast cancer; Invasion; IκB kinase; Tumor necrosis factor alpha.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Breast Neoplasms / drug therapy*
Breast Neoplasms / genetics
Breast Neoplasms / metabolism
Breast Neoplasms / pathology
Cell Line, Tumor
Chalcones / chemical synthesis
Chalcones / chemistry
Chalcones / pharmacology*
Chemokine CXCL1 / biosynthesis*
Chemokine CXCL1 / genetics
Dose-Response Relationship, Drug
Female
Humans
Molecular Structure
NF-kappa B / antagonists & inhibitors*
NF-kappa B / metabolism
Neoplasm Invasiveness / prevention & control*
RNA, Messenger / genetics
Structure-Activity Relationship
Tumor Necrosis Factor-alpha / metabolism*

Substances

2-hydroxy-3',5,5'-trimethoxychalcone
Chalcones
Chemokine CXCL1
NF-kappa B
RNA, Messenger
Tumor Necrosis Factor-alpha