Licochalcone A induces apoptosis in malignant pleural mesothelioma through downregulation of Sp1 and subsequent activation of mitochondria-related apoptotic pathway

Kim,Ka Hwi; Yoon,Goo; Cho,Jung Jae; Cho,Jin Hyoung; Cho,Young Sik; Chae,Jung-Il; Shim,Jung-Hyun

doi:10.3892/ijo.2015.2839

Licochalcone A induces apoptosis in malignant pleural mesothelioma through downregulation of Sp1 and subsequent activation of mitochondria-related apoptotic pathway

Authors:
- Ka Hwi Kim
- Goo Yoon
- Jung Jae Cho
- Jin Hyoung Cho
- Young Sik Cho
- Jung-Il Chae
- Jung-Hyun Shim
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Affiliations: Natural Medicine Research Institute, Department of Pharmacy, College of Pharmacy, Mokpo National University, Jeonnam 534-729, Republic of Korea, Department of Oral Pharmacology, School of Dentistry and Institute of Oral Bioscience, BK21 plus, Chonbuk National University, Jeonju 651-756, Republic of Korea, College of Pharmacy, Keimyung University, 1000 Sindang-dong, Dalseo-gu, Daegu 704-701, Republic of Korea
Published online on: January 13, 2015 https://doi.org/10.3892/ijo.2015.2839
Pages: 1385-1392

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Abstract

Licochalcone A (LCA) is a natural product derived from the roots of Glycyrrhiza inflata exhibiting a wide range of bioactivities such as antitumor, anti-oxidant and anti-bacterial effects. Malignant pleural mesothelioma (MPM) is an extremely aggressive type of cancer with a poor prognosis because of its rapid progression. However, LCA has not been investigated concerning its effects on MPM. Preliminarily, we observed that LCA negatively modulated not only cell growth, but also specificity protein 1 (Sp1) expression in MSTO-211H and H28 cell lines. It was found that IC50 values of LCA for growth inhibition of MSTO-211H and H28 cells were approximately 26 and 30 µM, respectively. Consistent with downregulation of Sp1, expression of Sp1 regulatory proteins such as Cyclin D1, Mcl-1 and Survivin was substantially diminished. Mechanistically, LCA triggered the mitochondrial apoptotic pathway by affecting the ratio of mitochondrial proapoptotic Bax to anti-apoptotic Bcl-xL. Bid induced loss of mitochondrial membrane potential, eventually leading to multi-caspase activation and increased sub-G1 population. Moreover, nuclear staining with DAPI highlighted nuclear condensation and fragmentation of apoptotic features. Flow cytometry analyses after staining cells with Annexin V and propiodium iodide corroborated LCA-mediated apoptotic cell death of MPM cells. In conclusion, these results present that LCA may be a potential bioactive material to control human MPM cells by apoptosis via the downregulation of Sp1.

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