Blockage of epithelial to mesenchymal transition and upregulation of let 7b are critically involved in ursolic acid induced apoptosis in malignant mesothelioma cell

Our plain-English summary of Blockage of epithelial to mesenchymal transition and upregulation of let 7b are critically involved in ursolic acid induced apoptosis in malignant mesothelioma cell, by E.J. Sohn, G. Won, J. Lee, et al (International Journal of Biological Sciences, 2016).

The study

• Authors: E.J. Sohn, G. Won, J. Lee, S.W. Yoon, I. Lee, H.J. Kim, S.H. Kim
• Journal: International Journal of Biological Sciences
• Published: 2016;12(11):1279-1288
• Cited by: 30 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPN), which is caused by asbestos exposure, is one of aggressive lung tumors. In the present study, we elucidated the anti-tumor mechanism of ursolic acid in malignant mesotheliomas. Ursolic acid significantly exerted cytotoxicity in a time and dose dependent manner in H28, H2452 and MSTO-211H mesothelioma cells and inhibited cell proliferation by colony formation assay in a dose-dependent fashion. Also, ursolic acid treatment accumulated the sub-G1 population, attenuated the expression of procapase 9, cyclin D1, pAKT, p-glycogen synthase kinase 3-alpha/beta (pGSK3α/β), β-catenin and nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB) and also cleaved caspase 3 and poly (ADP-ribose) polymerase (PARP) in mesothelioma cells. Furthermore, ursolic acid treatment blocked epithelial and mesenchymal transition (EMT) molecules by activating E-cadherin as an epithelial marker and attenuating Vimentin, and Twist as mesenchymal molecules. Interestingly, miRNA array revealed that 23 miRNAs (>2 folds) including let-7b and miRNA3613-5p, miRNA134 and miRNA196b were significantly upregulated while 33 miRNAs were downregulated in ursolic acid treated H2452 cells. Furthermore, overexpression of let 7b using let-7b mimics enhanced the antitumor effect of ursolic acid to attenuate the expression of procaspases 3, pro-PARP, pAKT, β-catenin and Twist and increase sub-G1 accumulation in H2452 mesothelioma cells. Overall, our findings suggest that ursolic acid induces apoptosis via inhibition of EMT and activation of let7b in mesothelioma cells as a potent chemotherapeutic agent for treatment of malignant mesotheliomas.

In plain English

This was a laboratory study of three human mesothelioma cell lines (H28, H2452 and MSTO-211H). No patients or animals were studied, and the cells were not exposed to asbestos. The authors tested ursolic acid, found in many plants and fruits, alongside other natural compounds. Ursolic acid showed significant toxicity to H28 and H2452 cells compared with the other compounds, and its toxicity depended on time and dose in all three cell lines. It reduced colony growth of H2452 and H28 cells and increased signs of programmed cell death, including cleavage of the proteins PARP and caspase 3. It raised E-cadherin in H2452 and H28 cells and lowered several markers of epithelial to mesenchymal transition (EMT), linked to cancer spread. A screen found the small regulatory RNA let-7b raised 7.358 fold; the results place this screen in H2452 cells, but the methods say H28 cells. Adding extra let-7b strengthened ursolic acid's effects, and blocking let-7b reduced its toxicity. The authors concluded that inhibition of EMT and activation of let-7b are critically involved in ursolic acid induced cell death in mesothelioma cells.

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 cultured mesothelioma cell lines
• Who was studied: Three commercially obtained human mesothelioma cell lines (H28, H2452 and MSTO-211H); no human participants or animals
• Exposure: Ursolic acid (and, for comparison, apigenin, galbanic acid, gallotannin, decursin and PGG) at 0 to 80 μM for 24 hours in toxicity tests, with other tests at up to 40 μM; no asbestos exposure was studied
• Main results:
  • Ursolic acid showed significant toxicity to H28 and H2452 cells compared with the other compounds tested
  • Toxicity of ursolic acid depended on time and dose in all three cell lines
  • Ursolic acid increased the sub-G1 cell fraction (a sign of cell death) in all three cell lines compared with untreated cells
  • Ursolic acid caused cleavage of PARP and caspase 3 and lowered procaspase-3 and -9 in a dose-dependent way in all three cell lines
  • Ursolic acid raised E-cadherin in H2452 and H28 cells and lowered mesenchymal markers in H2452 and MSTO-211H cells; Vimentin was not detected in H28 cells
  • The microRNA array showed upregulation of let-7b (7.358 fold), miR 3613-5p (4.133 fold), miR 134 (3.833 fold) and miR 196b (3.354 fold), with 33 microRNAs reported downregulated; the results describe these as ursolic acid treated H2452 cells, though the methods say the RNA came from H28 cells
  • In H2452 cells, a let-7b mimic strengthened ursolic acid's effects on PARP and caspase 3 cleavage and on p-AKT, β-catenin and Twist
  • A let-7b inhibitor blocked the toxicity of ursolic acid in H2452 cells
• The authors' conclusion: The authors concluded that inhibition of EMT and activation of let-7b are critically involved in ursolic acid induced apoptosis in mesothelioma cells

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, Malignant Mesothelioma, Pleural Mesothelioma, Asbestos Exposure, Mesothelioma.

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