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

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.

Keywords: Cell cycle; Cisplatin; JNK; MAPK; Mesothelioma; Quercetin; p38.

Fig. 1

mRNA levels of cell cycle regulators. CDI, cyclin and cyclin dependent kinase(CDK) expressions in SPC212 cells treated with QU and QU + CIS. Two-fold or more differences compared to control cells were evaluated by RT-PCR array. Group 1: DMSO Control versus Quercetin; Group 2: DMSO control versus Quercetin + Cisplatin

Fig. 2

mRNA levels of JNK/SAPK and p38MAPK pathway members. Cells treated with 50 μM QU and 50 μM QU + 5 μg/ml CIS. Two-fold or more differences compared to control cells were evaluated by RT²-PCR array Group 1: DMSO Control versus Quercetin; Group 2: DMSO control versus Quercetin + Cisplatin

Fig. 3

mRNA levels of MAPK and survival pathway members. Two-fold or more differences compared to control cells were evaluated by RT²-PCR array. Group 1: DMSO Control versus Quercetin; Group 2: DMSOcontrol versus Quercetin + Cisplatin

Fig. 4

Phosphorylation and total protein levels of MAPKs. Cells were treated with 5 μg/ml CIS, 50 μM QU or both for a series of time and 15 μg their proteins were analysed by Western Blotting as described in material methods. The experiments were repeated at least three times with similar results