Role of transcription factor Sp1 in the quercetin-mediated inhibitory effect on human malignant pleural mesothelioma

Our plain-English summary of Role of transcription factor Sp1 in the quercetin-mediated inhibitory effect on human malignant pleural mesothelioma, by J.I. Chae, J.H. Cho, K.A. Lee, et al (International Journal of Molecular Medicine, 2012).

The study

• Authors: J.I. Chae, J.H. Cho, K.A. Lee, N.J. Choi, K.S. Seo, S.B. Kim, S.H. Lee, J.H. Shim
• Journal: International Journal of Molecular Medicine
• Published: 2012;30(4):835-41
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Quercetin (Qu) is found in plants, including red onions and in the skins of red apples, and induces the apoptosis of certain malignant cells. However, no report has been issued on the apoptotic effect of Qu on human malignant pleural mesothelioma. In the present study, it was found that MSTO-211H mesothelioma cell viability was reduced and apoptotic cell death was increased by Qu (20-80 µM), which was found to have an IC₅₀ of 58 µM. In addition, Qu increased the sub-G₁ cell population, and was found to interact with specificity protein 1 (Sp1) and significantly suppressed its expression at the protein and mRNA levels. Furthermore, Qu modulated the levels of Sp1 regulatory genes, such as cyclin D1, myeloid cell leukemia (Mcl)-1 and survivin in MSTO-211H cells. Apoptotic signaling cascades were activated by the cleavage of Bid, caspase-3 and PARP, and by the downregulation of Bcl-xL and the upregulation of Bax in MSTO-211H cells. Our results strongly suggest that Sp1 be considered as a novel molecular target of Qu in human malignant pleural mesothelioma.

In plain English

This was a laboratory study of human malignant pleural mesothelioma cells. No patients or animals were studied, and asbestos exposure was not part of the work. The authors treated a mesothelioma cell line called MSTO-211H with quercetin, a compound found in plants such as onions and apples, at 20 to 80 µM. Quercetin reduced cell viability, with an IC50 (the concentration that cut viability by half) of 58 µM after 48 hours. The share of cells in the sub-G1 phase, a sign of cell death, rose from 25 to 50% across the 20-80 µM range. In a binding test, quercetin attached to a protein called Sp1, and treatment lowered Sp1 protein and mRNA levels. Quercetin also lowered levels of cyclin D1, Mcl-1 and survivin, which are genes controlled by Sp1. It also changed several proteins involved in programmed cell death (apoptosis). The authors concluded that Sp1 should be considered a therapeutic target, and that quercetin should be considered a drug or natural supplement candidate for preventing malignant pleural mesothelioma. The study did not test this in people.

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) cell culture experiment
• Who was studied: MSTO-211H human malignant pleural mesothelioma cells obtained from the American Tissue Culture Collection; a second mesothelioma cell line, HT28, was mentioned with data not shown
• Exposure: Quercetin (a plant flavonoid) at 20-80 µM, applied to cells for various times (mainly 24 or 48 h). Asbestos exposure was not studied.
• Main results:
  • Quercetin reduced viability of MSTO-211H cells with an IC50 of 58 µM at 48 h
  • In HT28 cells (another mesothelioma cell line), the IC50 was approximately 73 µM at 48 h; these data were not shown
  • The proportion of MSTO-211H cells in sub-G1 phase rose from 25 to 50% with 20-80 µM quercetin
  • Quercetin bound to Sp1 in MSTO-211H cell lysates
  • Quercetin at 20, 40 and 80 µM lowered Sp1 protein and mRNA levels, and reduced Sp1 protein over time from 0 to 48 h
  • Quercetin decreased protein levels of the Sp1-regulated genes cyclin D1, Mcl-1 and survivin
  • Quercetin activated Bid, caspase-3 and PARP, decreased Bcl-xL and increased Bax in MSTO-211H cells
• The authors' conclusion: The authors concluded that Sp1 should be considered a therapeutic target in malignant pleural mesothelioma, and that quercetin should be considered a drug or natural supplement candidate for its prevention

Topics

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

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

Related studies

• Nrf2 Expression and Apoptosis in Quercetin-treated Malignant Mesothelioma Cells — Y.J. Lee, D.M. Lee, et al. (2015)
• The flavonoid resveratrol suppresses growth of human malignant pleural mesothelioma cells through direct inhibition of specificity protein 1 — K.A. Lee, Y.J. Lee, et al. (2012)
• Manumycin A induces apoptosis in malignant pleural mesothelioma through regulation of Sp1 and activation of the mitochondria-related apoptotic pathway — K.H. Kim, J.I. Chae, et al. (2016)
• Licochalcone A induces apoptosis in malignant pleural mesothelioma through downregulation of Sp1 and subsequent activation of mitochondria-related apoptotic pathway — K.H. Kim, G. Yoon, et al. (2015)
• The tocotrienol-rich fraction from rice bran enhances cisplatin-induced cytotoxicity in human mesothelioma H28 cells — K. Nakashima, N. Virgona, et al. (2010)
• BRCA1 is an essential mediator of vinorelbine-induced apoptosis in mesothelioma — S. Busacca, M. Sheaff, et al. (2012)

Browse more research in International Journal of Molecular Medicine, or return to medical research.