Synergistic anti-cancer effects of resveratrol and chemotherapeutic agent clofarabine against human malignant mesothelioma MSTO-211H cells

Our plain-English summary of Synergistic anti-cancer effects of resveratrol and chemotherapeutic agent clofarabine against human malignant mesothelioma MSTO-211H cells, by Y.J. Lee, Y.J. Lee, J.H. Im, et al (Food and Chemical Toxicology, 2013).

The study

• Authors: Y.J. Lee, Y.J. Lee, J.H. Im, S.Y. Won, Y.B. Kim, M.K. Cho, H.S. Nam, Y.J. Choi, S.H. Lee
• Journal: Food and Chemical Toxicology
• Published: 2013;52:61-8
• Cited by: 40 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Dietary phytochemicals as adjuvants have been suggested to play important roles in enhancing chemotherapeutic potential owing to multitargeted chemopreventive properties and lack of substantial toxicity. Here, we investigated the efficacy of the combined treatment of various phytochemicals with the anticancer drug clofarabine in malignant mesothelioma MSTO-211H cells and normal mesothelial MeT-5A cells. The combined treatment of resveratrol and clofarabine produced a synergistic antiproliferative effect in MSTO-211H cells, but not in MeT-5A cells. In MSTO-211H cells, the nuclear accumulation of Sp1 and the levels of p-Akt, Sp1, c-Met, cyclin D1, and p21 were effectively decreased by the combined treatment of them. In combination with clofarabine, the ability of resveratrol to reduce the contents of Sp1 and its target gene products was also evident in a time- and dose-dependent experiment. The inhibition of phosphoinositide 3-kinase using Ly294002 augmented a decrease in the p21 level induced by their combination, but it showed no significant effects on expression of Sp1 and cyclin D1. Taken together, the data provide evidence that the synergistic antiproliferative effect of resveratrol and clofarabine is linked to the inhibition of Akt and Sp1 activities, and suggest that this combination may have therapeutic value in treatment of malignant mesothelioma.

Copyright © 2012 Elsevier Ltd. All rights reserved.

In plain English

This was a laboratory study using cells grown in culture, not patients. The authors tested whether four plant-derived compounds (resveratrol, quercetin, cafestol and sulforaphane) added to the effect of the cancer drug clofarabine. They used a human malignant mesothelioma cell line, MSTO-211H, and compared it with a normal mesothelial cell line, MeT-5A. Of the four compounds combined with clofarabine, only resveratrol gave a significantly greater effect. After 48 hours, resveratrol alone at 5, 10, 15 and 20 micromolar reduced mesothelioma cell proliferation by about 4.9%, 10.5%, 13% and 20%. The same doses combined with 40 nM clofarabine reduced it by about 24.7%, 30.3%, 47.8% and 49.5%. Combination index values were below 1, which the authors defined as synergy. The normal MeT-5A cells showed little toxicity from the combination. In the mesothelioma cells, the combination lowered levels of the proteins Sp1, c-Met, cyclin D1 and p21, and of phosphorylated Akt. The authors concluded that the synergy may be caused at least in part by these changes. They stated that further cell or animal studies are needed.

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 measuring cell viability and protein levels
• Who was studied: Human malignant mesothelioma cell line MSTO-211H and human normal mesothelial cell line MeT-5A, obtained from the American Type Culture Collection; results from three independent experiments
• Exposure: Plant-derived compounds resveratrol, quercetin, cafestol and sulforaphane, alone or combined with the chemotherapy drug clofarabine (40 nM). Resveratrol was given at 5 to 20 micromolar. No asbestos exposure was studied.
• Main results:
  • In MSTO-211H cells, the concentrations causing 10% growth inhibition (IC10) were 10 micromolar for resveratrol, 18 for quercetin, 22 for sulforaphane and 30 for cafestol
  • Clofarabine was non-toxic to MSTO-211H cells up to 40 nM (IC10 = 42 nM), while 80 nM inhibited cell growth
  • Among the four compounds combined with clofarabine, only resveratrol produced a significant combined effect. For 10 micromolar resveratrol plus 40 nM clofarabine for 48 h, the article reports cell proliferation of 69.7%, versus 90% for resveratrol alone and 91.3% for clofarabine alone
  • In MSTO-211H cells over 48 h, resveratrol alone at 5, 10, 15 and 20 micromolar reduced proliferation by about 4.9%, 10.5%, 13% and 20%
  • In MSTO-211H cells, the same resveratrol doses combined with 40 nM clofarabine reduced proliferation by about 24.7%, 30.3%, 47.8% and 49.5%
  • Combination index values were 0.71, 0.71, 0.70 and 0.71 at 24 h and 0.96, 0.94, 0.44 and 0.46 at 48 h. The authors defined values below 1 as synergy.
  • Greater synergy was seen with 15 micromolar resveratrol plus 40 nM clofarabine in MSTO-211H cells. Normal MeT-5A cells showed little toxicity from the combination.
  • The combination inhibited the movement of Sp1 into the cell nucleus in MSTO-211H cells
  • Levels of Sp1, c-Met, cyclin D1 and p21 were decreased by the combination only in MSTO-211H cells
  • In MSTO-211H cells, phosphorylated Akt fell within 30 minutes of the combination treatment and stayed below control levels over 24 h
  • Pretreatment with the PI3K inhibitor Ly294002 increased the combination's lowering of p21 but had no significant effect on Sp1 or cyclin D1
• The authors' conclusion: The authors concluded that resveratrol and clofarabine had a synergistic anti-proliferative effect in MSTO-211H cells. They suggested this may be caused at least in part by inhibition of Akt phosphorylation, suppression of Sp1 activation, and down-regulation of c-Met, cyclin D1 and p21.
• Limitations the authors state:
  • The authors stated that the possible roles of Akt and Sp1 in the synergy must be validated by further in vitro or in vivo animal studies

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, MeT-5A Cells.

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