Abstract
BackgroundMalignant 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.MethodsIn present work, 84 genes involved in cell growth and proliferation have analysed by using RT2-PCR array system and protein profile of mitogen activated protein kinase (MAPK) family proteins investigated by western blots.ResultsOur 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.ConclusionThis research has clarified our previous results and detailed mechanism of anti-carcinogenic potential of Quercetin alone and incombination with Cisplatin on malignant mesothelioma cells.
Highlights
Malignant mesothelioma is a locally aggressive and highly lethal neoplasm of pleural, peritoneal and pericardial mesothelial cells without successful therapy
The effects of QU + CIS on cell cycle and mitogen activated protein kinase (MAPK) pathway genes To investigate whether QU + CIS changed gene expressions of SPC212 cells, we exposed cells with QU + CIS (50 μM + 5 μg/mL) and QU (50 μM)
The reverse transcriptase-real time polymerase chain reaction (RT2-PCR) array revealed that compared to untreated cells expression of cylin dependent kinase inhibitor (CDI) genes [CDKN1A (p21), CDKN1B (p27), CDKN1C (p57), CDKN2A (p16) and CDKN2B (p15),] were up regulated in QU + CIS and QU treated cells respectively
Summary
Malignant mesothelioma is a locally aggressive and highly lethal neoplasm of pleural, peritoneal and pericardial mesothelial cells without successful therapy. We reported that Quercetin in combination with Cisplatin inhibits cell proliferation and activates caspase-9 and -3 enzymes in different malignant mesothelioma cell lines. Quercetin + Cisplatin lead to accumulation of both SPC111 and SPC212 cell lines in S phase. Malignant mesothelioma (MM) is a neoplastic proliferation that develops from pleural, peritoneal or rarely pericardial mesothelial cells [1]. Platinum drug ‘Cisplatin’ (CIS) is conventionally employed against to MM [1]. The combination therapies with CIS & Pemetrexed or Raltitrexed are currently used to treat MM patients [3]. It is required to improve alternative strategies or drugs since resistance of cancer cells to CIS therapy [4]. Quercetin (QU) is a plant derived flavonoid exhibiting anti-proliferative, Demiroglu-Zergeroglu et al BMC Complementary and Alternative Medicine (2016) 16:281
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