Quercetin and Cisplatin combined treatment altered cell cycle and mitogen activated protein kinase expressions in malignant mesotelioma cells

Our plain-English summary of Quercetin and Cisplatin combined treatment altered cell cycle and mitogen activated protein kinase expressions in malignant mesotelioma cells, by A. Demiroglu-Zergeroglu, E. Ergene, N. Ayvali, et al (BMC Complementary and Alternative Medicine, 2016).

The study

• Authors: A. Demiroglu-Zergeroglu, E. Ergene, N. Ayvali, V. Kuete, H. Sivas
• Journal: BMC Complementary and Alternative Medicine
• Published: 2016;16(1):281
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Malignant mesothelioma is a locally aggressive and highly lethal neoplasm of pleural, peritoneal and pericardial mesothelial cells without successful therapy. Previously, we reported that Quercetin in combination with Cisplatin inhibits cell proliferation and activates caspase-9 and -3 enzymes in different malignant mesothelioma cell lines. Moreover, Quercetin + Cisplatin lead to accumulation of both SPC111 and SPC212 cell lines in S phase.

Methods: In present work, 84 genes involved in cell growth and proliferation have analysed by using RT(2)-PCR array system and protein profile of mitogen activated protein kinase (MAPK) family proteins investigated by western blots.

Results: Our results showed that Quercetin and Quercetin + Cisplatin modulated gene expression of cyclins, cyclin dependent kinases and cyclin dependent kinases inhibitors. In addition genes involved in JNK, p38 and MAPK/ERK pathways were up regulated. Moreover, while p38 and JNK phosphorylations were increased, ERK phosphorylations were decreased after using Quercetin + Cisplatin.

Conclusion: This research has clarified our previous results and detailed mechanism of anti-carcinogenic potential of Quercetin alone and incombination with Cisplatin on malignant mesothelioma cells.

In plain English

This was a laboratory study of cancer cells, not of people or of asbestos exposure. The authors treated one human malignant mesothelioma cell line, SPC212, with quercetin (a plant flavonoid, 50 μM), the chemotherapy drug cisplatin (5 μg/mL), or both, and compared them with solvent-treated control cells. They measured 84 genes linked to MAP kinase signalling and several signalling proteins. Quercetin plus cisplatin raised expression of the cell-cycle brake genes CDKN1A, CDKN1B, CDKN2A and CDKN2B (cyclin dependent kinase inhibitors), while quercetin alone raised CDKN1C. The combination also raised cyclin genes and CDK2 more than two-fold, which the authors suggested may reflect resistance to cisplatin. Many signalling genes rose; two, MNK1 and TP53, fell with the combination. At the protein level after treatment, ERK activation fell, while JNK and p38 activation rose in the first 24 hours and then fell. The authors concluded that the combination stopped the cells in the S phase of their growth cycle and that the cells underwent apoptosis (programmed cell death), probably involving the JNK and p38 pathways.

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: gene-expression array (RT2-PCR) and western blots on drug-treated mesothelioma cells
• Who was studied: One human malignant mesothelioma cell line, SPC212, derived from a tumour of mixed histology from a female patient and obtained from the University of Fribourg, Switzerland; no human participants
• Exposure: No asbestos exposure was studied (asbestos is mentioned only as background). Cells were treated with quercetin (50 μM), cisplatin (5 μg/mL), or both, compared with a DMSO solvent control; 48 hours for gene analysis and 12, 24 and 48 hours for protein analysis
• Main results:
  • In quercetin + cisplatin treated cells, expression of the cyclin dependent kinase inhibitor genes CDKN1A, CDKN1B, CDKN2A and CDKN2B was up regulated
  • In cells treated with quercetin alone, expression of the cyclin dependent kinase inhibitor gene CDKN1C was up regulated, along with MEK6 and MAPK11
  • In quercetin + cisplatin treated cells, cyclin genes and CDK2 gene expression rose more than two-fold
  • The authors interpreted the unexpected rise in CDK2 and cyclin genes as suggesting resistance of the cells to cisplatin
  • Quercetin + cisplatin increased expression of JNK/p38 pathway genes DLK, MAP3K4, MAP2K4, CDC42 and MAPK8IP2/JIP1 two-fold or more
  • Quercetin alone up regulated classical MAPK pathway genes two-fold or more
  • Only two genes were down regulated after quercetin + cisplatin: MNK1 and TP53 (p53)
  • At the protein level after treatment, ERK phosphorylation decreased, while JNK and p38 phosphorylation increased in the first 24 hours and then decreased
• The authors' conclusion: The authors concluded that quercetin + cisplatin induced S phase arrest regulated by almost all cyclin dependent kinase inhibitors in SPC212 cells, and that the cells underwent apoptosis probably involving the JNK and p38 MAPK pathways, even though survival/resistance pathways were also activated

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: Cisplatin, Mesothelioma, Neoplasm, Pericardial, Mesothelial Cells, Carcinogenic.

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