Natural diterpenes from coffee, cafestol and kahweol induce apoptosis through regulation of specificity protein 1 expression in human malignant pleural mesothelioma

Our plain-English summary of Natural diterpenes from coffee, cafestol and kahweol induce apoptosis through regulation of specificity protein 1 expression in human malignant pleural mesothelioma, by K.A. Lee, J.I. Chae, J.H. Shim (Journal of Biomedical Science, 2012).

The study

• Authors: K.A. Lee, J.I. Chae, J.H. Shim
• Journal: Journal of Biomedical Science
• Published: 2012;19(1):60
• Cited by: 56 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Malignant pleural mesothelioma (MPM) is a highly aggressive cancer with a very poor prognosis. Several clinical studies such as immunotherapy, gene therapy and molecular targeting agents have been tried for treatment of malignant mesothelioma, however, there is no application for effective clinical treatment. Coffee has various biological functions such as anti-oxidant, anti-inflammatory, anti-mutagenic and anti-carcinogenic activities. The therapeutic activities of the bioactive compounds in coffee was sugested to influence intracellular signaling of MPM. Regarding to the cancer-related functions, In this study, suppression of Sp1 protein level followed by induction of MSTO-211H cell apoptosis by cafestol and kahweol were investigated in oreder to determine Sp1's potential as a significant target for human MPM therapy as well.

Methods: Cells were treated separately with final concentration of cafestol and kahweol and the results were analyzed by MTS assay, DAPI staining, PI staining, luciferase assay, RT-PCR, and immunoblotting.

Results: Viability of MSTO-211H and H28 cells were decreased, and apoptotic cell death was increased in MSTO-211H as a result of cafestol and kahweol treatment. Cafestol and kahweol increased Sub-G1 population and nuclear condensation in MSTO-211H cells. Roles of Sp1 in cell proliferation and apoptosis of the MSTO-211H cells by the Sp1 inhibitor of Mithramycin A were previously confirmed. Cafestol and kahweol significantly suppressed Sp1 protein levels. Kahweol slightly attenuated Sp1 mRNA, while Cafestol did not affect in MSTO-211H cells. Cafestol and kahweol modulated the promoter activity and protein expression level of the Sp1 regulatory genes including Cyclin D1, Mcl-1, and Survivin in mesothelioma cells. Apoptosis signaling cascade was activated by cleavages of Bid, Caspase-3, and PARP with cafestol and by upregulation of Bax, and downregulation of Bcl-xl by kahweol.

Conclusions: Sp1 can be a novel molecular target of cafestol and kahweol in human MPM.

In plain English

This was a laboratory study of human malignant pleural mesothelioma cells grown in dishes. It did not involve patients, animals or asbestos exposure. The authors treated two mesothelioma cell lines, MSTO-211H and H28, with cafestol and kahweol, two compounds found in coffee oil. They also tested mithramycin A, a known blocker of a protein called Sp1. Cell viability in both cell lines fell as the dose of the coffee compounds increased. In MSTO-211H cells, the compounds increased signs of apoptosis (programmed cell death). After 48 hours, the share of cells in the sub-G1 fraction, a marker of dying cells, was 12 to 30% with cafestol and 10 to 31% with kahweol. Both compounds lowered Sp1 protein. Kahweol slightly lowered Sp1 messenger RNA, while cafestol did not. The compounds also reduced the activity of Sp1-controlled genes and changed apoptosis-related proteins. The authors concluded that cafestol and kahweol are potential cancer drugs or add-on treatments for this cancer. They said animal studies are needed to test safety and effectiveness.

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: Two human mesothelioma cell lines, MSTO-211H and H28, obtained from the American Tissue Culture Collection. Most experiments after the viability tests used MSTO-211H cells only.
• Exposure: Treatment with the coffee diterpenes cafestol (30, 60 and 90 μM) and kahweol (20, 40 and 60 μM), compared with untreated (DMSO) cells, mainly for 48 hours. The Sp1 inhibitor mithramycin A (10 to 40 μM) was also tested. Asbestos exposure was not studied.
• Main results:
  • Viability of MSTO-211H and H28 cells decreased with increasing doses of cafestol and kahweol at 24 and 48 hours.
  • In MSTO-211H cells, cafestol and kahweol increased nuclear condensation (a sign of apoptosis) compared with the control group.
  • The sub-G1 (dying-cell) population was 12 to 30% in cafestol-treated MSTO-211H cells and 10 to 31% in kahweol-treated MSTO-211H cells.
  • Both cafestol and kahweol suppressed Sp1 protein in MSTO-211H cells.
  • Cafestol did not suppress Sp1 mRNA in MSTO-211H cells; kahweol slightly inhibited it.
  • Cafestol and kahweol reduced the promoter activity of the Sp1-regulated genes Cyclin D1, Mcl-1 and Survivin.
  • In treated MSTO-211H cells, Bid, Caspase-3 and PARP were activated, Bcl-xl decreased and Bax increased.
  • Mithramycin A at 10 to 40 μM decreased MSTO-211H cell viability.
• The authors' conclusion: The authors concluded that Sp1 can be used as a therapeutic target and that cafestol and kahweol are potential cancer drugs or adjuvants for malignant pleural mesothelioma.
• Limitations the authors state:
  • In vivo studies are needed to establish safety and effectiveness for clinical use.
  • The inhibitory mechanisms of cafestol and kahweol still need definite verification.

Topics

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

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

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