Abstract

 
 
 
 Purpose: To study the anti-proliferative potential of paeonol against lung cancer cells, and investigate its mechanism of action.
 Methods: Cell viability after paeonol treatment was determined with 3-(4,5-dimethylthiazol-2yl)2,5- diphenyltetrazolium bromide (MTT) assay, while paeonol- and TRAIL-mediated apoptosis was assayed using flow cytometry. Western blotting was used to assay the protein expression levels of phosphorylated JNK and ERK1/2, as well as protein expressions of pro-apoptotic factors/death receptors. 2′,7′-Dichlorodihydrofluorescein diacetate (H2DCFDA) staining and flow cytometry were used to monitor paeonol-induced reactive oxygen species (ROS) in the cells.
 Results: Paeonol treatment markedly reduced the proliferations of H1975 and BGC823 cells (p < 0.05). In H1975 and BGC823 cells, paeonol/TRAIL combination increased apoptosis to 88.43 and 87.21 %, respectively (p < 0.05). The levels of death receptor 4 (DR4) and death receptor 5 (DR5) were increased significantly by paeonol, relative to the control (p < 0.05). Paeonol also reduced the levels of decoy receptor-1 (DcR1) and decoy receptor-2 (DcR2), and increased the expression of CHOP (p < 0.05). The protein expression levels of survivin, Bcl-2, cFLIP and Bcl-xL were decreased, while protein levels of caspase3, caspase-8 and caspase-9 were upregulated by paeonol. Moreover, paeonol significantly upregulated p-ERK and p-JNK in H1975 and BGC823 cells, and also increased ROS levels, when compared to control (p < 0.05).
 Conclusion: Paeonol exerts anti-proliferative potential on lung cancer cells through upregulation of death receptors, activation of JNK/ERK-CHOP pathway and generation of ROS. Therefore, paeonol has a therapeutic potential for the management of lung cancer.
 
 
 
Highlights
Lung cancer is a leading cause of mortality among various types of cancers globally, notwithstanding huge advancement in chemotherapy and diagnostic techniques [1]
tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) influences the activities of decoy receptor (DcR)-1, decoy receptor-2 (DcR2) and the receptor protein osteoprotegerin [6]
The present study investigated the lung cancer-sensitizing potential of paeonol to TRAIL treatment
Summary
Lung cancer is a leading cause of mortality among various types of cancers globally, notwithstanding huge advancement in chemotherapy and diagnostic techniques [1]. Studies have revealed down-regulated DR4 and DR5 expressions and enhanced decoy receptor levels in carcinoma cells resistant to TRAIL [8, 9]. Apoptosis of H1975 and BGC823 cells was analysed with a flow cytometer using Annexin V-FITC/PI kit. The expressions of DR4 and DR5 in H1975 and BGC823 cells after paeonol treatment were assayed using flow cytometry [15]. The cells were incubated for 72 h with 8 μM paeonol or DMSO as control and lysed on ice for 45 min by incubation with lysis buffer. The H1975 and BGC823 cells were incubated for 72 h with 8 μM paeonol or with DMSO (control), followed by incubation at 37°C for 20 min with DCF-DA (20 μM). Differences were taken as statistically significant at p < 0.05
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