Thiazolidinediones Regulate the Level of ABC Transporters Expression on Lung Cancer Cells

Abstract

SummaryATP binding cassette (ABC) transporters related to multidrug resistance (MDR) actively effl ux various xenobio tics from the cells across the cell membrane and decrease a drug's effi ciency. Lung cancer is the leading cause of death among all types of cancer in the Czech Republic, and its incidence is still rising. Ciglitazone, rosiglitazone and troglitazone belonging to PPAR-γ agonist family (formerly used in diabetes mellitus treatment) were selected to investigate their capability to infl uence expression of ABC transporters on lung cancer cells. Therefore, the eff ect of PPAR-γ of agonists on transcription of following ABC transporters was investigated: multidrug resistance protein 1 (MDR1), multidrug resistance-associated protein 1 (MRP1), and breast cancer resistance protein (BCRP). We have investigated if these PPAR-γ agonists are substrates of ABC transporters using HL60 and HL60 derived cell lines (HL60-MDR1, HL60-MRP1, PLB-BCRP) by cytotoxicity test WST-1. We have mapped the changes in mRNA expression level of those transporters in A549 and HEK293 cells after PPAR-γ agonists treatment using quantitative reverse transcription real-time PCR (qRT-PCR). All three PPAR-γ agonists serve as substrates to at least one ABC transporter under study. PPAR-γ activation correlates with up-regulation of PTEN which may modulate the expression of ABC transporters through PI3K/ Akt signaling pathway. We have shown that rosiglitazone and troglitazone inhibit mRNA expression of MDR1 transporter in both cell lines whereas the expression of MRP1 in HEK293 cell was up-regulated after rosiglitazone treatment and the expression of MDR1 was upregulated after ciglitazone treatment.

Regioselective Glucuronidation of Diosmetin and Chrysoeriol by the Interplay of Glucuronidation and Transport in UGT1A9-Overexpressing HeLa Cells

“…Therefore, we used these A549 and HepG2 tumor cell lines to demonstrate the effects of diosmetin and chrysoeriol on cell viability with untreated and treated Ko143 inhibitor (Fig 8). Both A549 and HepG2 cells express BCRP [40,41]. A549 cells express UGT1A1, UGT1A3 and UGT2B7 [42], and HepG2 cells expresse UGT1A1, UGT1A6 and UGT1A9 [43].…”

Overexpression of tensin homolog deleted on chromosome ten (PTEN) by ciglitazone sensitizes doxorubicin‐resistance leukemia cancer cells to treatment

“…Troglitazone was also demonstrated to suppress the transcription of P‐gp in vincristine‐resistant gastric cancer cells . Konieczna et al showed that all three PPARγ agonists (ciglitazone, rosiglitazone, and troglitazone) served as substrates to at least one ABC transporter including P‐gp, BCRP, and multidrug resistance‐associated protein 1 (MRP1) . They have shown that these agonists inhibit mRNA expression of transporters in lung cancer cells.…”

Role of adipocytokines in endometrial cancer progression

“…Thiazolidinediones (TZDs) (rosiglitazone, pioglitazone) are also reported to increase adiponectin levels and decrease leptin, tumor necrosis factor-α (TNF-α), and IL-6 levels through modulatory mechanisms ( Garikapati et al, 2019 ; Biondo et al, 2020 ). Moreover, TZDs have played important roles in preventing progression of hepatocellular carcinoma (HCC) ( Arvind et al, 2021 ), colon cancer ( Yoon et al, 2020 ), and lung cancer ( Konieczna et al, 2015 ). Atorvastatin reduces cardiovascular mortality by increasing levels of adiponectin, which is involved in insulin resistance ( Koh et al, 2005 ; Ando et al, 2008 ).…”