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

Our plain-English summary of Licochalcone A induces apoptosis in malignant pleural mesothelioma through downregulation of Sp1 and subsequent activation of mitochondria-related apoptotic pathway, by K.H. Kim, G. Yoon, J.J. Cho, et al (International Journal of Oncology, 2015).

The study

• Authors: K.H. Kim, G. Yoon, J.J. Cho, J.H. Cho, Y.S. Cho, J.I. Chae, J.H. Shim
• Journal: International Journal of Oncology
• Published: 2015;46(3):1385-92
• Cited by: 28 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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.

In plain English

This was a laboratory study of human cancer cells grown in dishes. It did not study people or asbestos exposure. The authors purified licochalcone A, a compound from the roots of the licorice plant Glycyrrhiza inflata, and tested it on two purchased malignant pleural mesothelioma cell lines, MSTO-211H and H28. Cells were treated with 10, 20 or 40 micromolar (µM), mostly for 48 hours. Cell survival fell as the dose rose. At 40 µM, viability compared with DMSO-treated control cells was 8.4% for MSTO-211H cells and 41.0% for H28 cells. The concentration that halved growth was 26 µM for MSTO-211H and 30.4 µM for H28. Measures of programmed cell death (apoptosis) also rose. Late apoptotic cells increased from 2.8% to 47.1% in MSTO-211H and from 2.7% to 17.6% in H28. The compound lowered levels of a protein called Sp1 and of proteins Sp1 controls, and reduced the membrane potential of mitochondria, the cell's energy producers. The authors concluded that licochalcone A may be a potential material to control mesothelioma cells by apoptosis through lowering Sp1.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) experiment on human cancer cell lines
• Who was studied: Two human malignant pleural mesothelioma cell lines, MSTO-211H and H28, bought from the American Tissue Culture Collection; experiments done in triplicate
• Exposure: Licochalcone A (LCA) purified from the roots of Glycyrrhiza inflata, given at 10, 20 and 40 µM, mostly for 48 hours. A related compound, licochalcone E (LCE), was tested at 40 µM for comparison. No asbestos exposure was studied.
• Main results:
  • The concentration of LCA that halved growth (IC50) was 26 µM in MSTO-211H cells and 30.4 µM in H28 cells
  • MSTO-211H cell viability, as a percentage of DMSO-treated control cells, was 101.6%, 29.0% and 8.4% at 10, 20 and 40 µM LCA
  • H28 cell viability, as a percentage of DMSO-treated control cells, was 86.7%, 59.7% and 41.0% at 10, 20 and 40 µM LCA
  • The comparison compound LCE had weak cytotoxic activity in H28 cells and none in MSTO-211H cells at 48 hours
  • The sub-G1 fraction (a sign of dying cells) rose with dose: from 3.0% (plus or minus 0.7) to 34.7% (plus or minus 2.6) in MSTO-211H, and from 2.5% (plus or minus 0.7) to 43.2% (plus or minus 2.1) in H28
  • Late apoptotic cells (Annexin V staining) rose from 2.8% to 47.1% in MSTO-211H and from 2.7% to 17.6% in H28
  • LCA reduced Sp1 mRNA and protein in a dose-dependent manner, and reduced the Sp1 target proteins Cyclin D1, Mcl-1 and Survivin
  • Cells with depolarized mitochondrial membranes (loss of membrane potential) at 10, 20 and 40 µM were 38.7%, 51.9% and 72.1% in MSTO-211H, and 14.1%, 62.3% and 94.4% in H28
  • Multi-caspase activity at 10, 20 and 40 µM was 14.2%, 28.1% and 81.3% in MSTO-211H, and 16.7%, 32.1% and 37.9% in H28
  • BID, Bcl-xL, caspase-3 and PARP were decreased or cleaved, and the pro-apoptotic protein Bax was increased. CHOP, DR4 and DR5 were also increased.
• The authors' conclusion: The authors concluded that LCA may be a potential bioactive material to control human MPM cells by apoptosis via the downregulation of Sp1. They suggested it as a possible anticancer strategy for MPM patients with Sp1 overexpression.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Apoptosis, Pleural Mesothelioma, Prognosis.

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