The flavonoid resveratrol suppresses growth of human malignant pleural mesothelioma cells through direct inhibition of specificity protein 1

Our plain-English summary of The flavonoid resveratrol suppresses growth of human malignant pleural mesothelioma cells through direct inhibition of specificity protein 1, by K.A. Lee, Y.J. Lee, J.O. Ban, et al (International Journal of Molecular Medicine, 2012).

The study

• Authors: K.A. Lee, Y.J. Lee, J.O. Ban, Y.J. Lee, S.H. Lee, M.K. Cho, H.S. Nam, J.T. Hong, J.H. Shim
• Journal: International Journal of Molecular Medicine
• Published: 2012;30(1):21-7
• Cited by: 26 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Resveratrol (Res), from the skin of red grapes, induces apoptosis in some malignant cells, but there are no reports on the apoptotic effect of Res on human malignant pleural mesothelioma. We found that Res interacts with specificity protein 1 (Sp1). The IC50 for Res was 17 µM in MSTO-211H cells. Cell viability was decreased and apoptotic cell death was increased by Res (0-60 µM). Res increased the Sub-G1 population in MSTO-211H cells and significantly suppressed Sp1 protein levels, but not Sp1 mRNA levels. Res modulated the expression of Sp1 regulatory proteins including p21, p27, cyclin D1, Mcl-1 and survivin in mesothelioma cells. After treatment with Res, apoptosis signaling cascades were activated by the activation of Bid, Bim, caspase-3 and PARP, upregulation of Bax and downregulation of Bcl-xL. Res (20 mg/kg daily for 4 weeks) effectively suppressed tumor growth in vivo in BALB/c athymic (nu+/nu+) mice injected with MSTO-211H cells, an effect that was mediated by inhibition of Sp1 expression and induction of apoptotic cell death. Our results strongly suggest that Sp1 is a novel molecular target of Res in human malignant pleural mesothelioma.

In plain English

This was a laboratory study, not a study of people. The authors tested resveratrol, a natural compound found in red grape skins, on human malignant pleural mesothelioma cells (the MSTO-211H cell line) and on mice carrying tumors grown from those cells. The study did not examine asbestos exposure. In the cells, resveratrol reduced cell viability. The concentration that cut viability to about half that of untreated cells (the IC50) was about 17 µM after 48 hours. It increased signs of programmed cell death (apoptosis). It bound to a protein called specificity protein 1 (Sp1) and lowered Sp1 protein levels, though not Sp1 mRNA levels. In 10 mice per group, daily injections of 20 mg/kg resveratrol for 4 weeks left tumor volume at 60% of that in untreated mice. Body weight did not differ remarkably between the groups, and Sp1 was reduced in the treated tumors. The authors concluded that their results strongly suggest Sp1 is a novel molecular target of resveratrol in human malignant pleural mesothelioma.

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 experiment on a human mesothelioma cell line, plus an animal experiment (mouse xenograft model)
• Who was studied: Human malignant pleural mesothelioma cells (MSTO-211H line, from the American Tissue Culture Collection), and six-week-old male BALB/c athymic nude mice (10 per group) injected under the skin with these cells
• Exposure: Resveratrol: 20 to 90 µM in cell experiments. In mice, 20 mg/kg injected into the abdomen daily for 4 weeks, compared with saline (PBS) injections. Asbestos exposure was not studied.
• Main results:
  • In MSTO-211H cells, resveratrol reduced cell viability (measured relative to untreated controls), with an IC50 of about 17 µM after 48 hours of treatment
  • In another mesothelioma cell line (HT28), the IC50 was about 35 µM; the authors did not show these data
  • In MSTO-211H cells, the share of cells in the sub-G1 phase (a marker of dying cells) rose from 50 to 55% with 20-60 µM resveratrol
  • Resveratrol bound to Sp1 in lysates from MSTO-211H cells
  • At 30, 60 and 90 µM, resveratrol lowered Sp1 protein but not Sp1 mRNA levels in MSTO-211H cells
  • After resveratrol treatment, levels of the Sp1-regulated proteins p21, p27, cyclin D1, Mcl-1 and survivin fell significantly
  • In mesothelioma cells, resveratrol triggered apoptosis signals: cleavage of Bid, caspase-3 and PARP, more Bax and less Bcl-xL
  • In mice, tumor volume in the resveratrol-treated group (20 mg/kg) was 60% of tumor volume in the control group
  • Body weight changes did not differ remarkably between control and resveratrol-treated mice
  • Sp1 protein was significantly reduced in tumor tissue from resveratrol-treated mice
• The authors' conclusion: The authors concluded that their results strongly suggest Sp1 is a novel molecular target of resveratrol in human malignant pleural mesothelioma

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

• 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)
• Knockdown of Bcl-xL enhances growth-inhibiting and apoptosis-inducing effects of resveratrol and clofarabine in malignant mesothelioma H-2452 cells — Y.J. Lee, I.S. Hwang, et al. (2014)
• Synergistic anti-cancer effects of resveratrol and chemotherapeutic agent clofarabine against human malignant mesothelioma MSTO-211H cells — Y.J. Lee, Y.J. Lee, et al. (2013)
• Resveratrol and clofarabine induces a preferential apoptosis-activating effect on malignant mesothelioma cells by Mcl-1 down-regulation and caspase-3 activation — Y.J. Lee, Y.J. Lee, et al. (2015)
• Synergistic inhibition of mesothelioma cell growth by the combination of clofarabine and resveratrol involves Nrf2 downregulation — Y.J. Lee, J.H. Im, et al. (2012)
• Resveratrol contributes to chemosensitivity of malignant mesothelioma cells with activation of p53 — Y.J. Lee, I.S. Park, et al. (2014)

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