Abstract
We studied the effect of derrone (DR), one of the major compounds of unripe fruits of Cudrania tricuspidata, on cancer cell death. DR inhibited cell growth of various cancer cells, and that was partially associated with apoptosis in A549 cells. DR showed the autophagic features, such as the conversion of LC3-I to LC3-II, the formation of autophagosome and the downregulation of SQSTM1/p62 (p62). The treatment of autophagy inhibitor reversed DR-mediated cell death, suggesting that DR induces autophagic cell death. The increase of cytoplasmic Ca2+ and ROS by DR treatment significantly influences the formation of autophagosomes; however, only ROS scavengers significantly rescued the reduced cell viability. Additional results revealed that treatment of DR induces sustained phosphorylation of ERK and the inhibition of ERK phosphorylation using U0126 (ERK inhibitor) markedly attenuated DR-induced cell death. Overall, these results suggest that DR induces autophagic cell death through intracellular ROS and sustained ERK phosphorylation in A549 cells.
Highlights
Despite the improvement in many anticancer drugs, the mortality rate of lung cancer is still increasing [1]
We investigated molecular mechanisms involved in DR-induced cell death, focusing on autophagy and apoptosis in A549 cells
The IC50 values of DR against A549, H292, PC3 and HCT116 were 42.7 μM, 39.3 μM, 45.0 μM and 42.4 μM, respectively. These results indicate that DR reduces cell growth that are not limited to specific cancer cell lines
Summary
Despite the improvement in many anticancer drugs, the mortality rate of lung cancer is still increasing [1]. NSCLC accounts for approximately 80% of the lung cancer [2]. Treatment with NSCLC is attempted with radiation therapy, chemotherapy, target treatment, and bronchoscopy. Since the early 2000s, the development of target therapies that selectively attack cancer cells has been activated, and lung cancer target treatment drugs such as gefitinib (Iressa) and erlotinib (Tarceva) have been used [3,4,5]. Because the target therapies have problems of high cost and low stability, patients receiving treatment were limited. Many scientists continue to make efforts to develop new lung cancer drugs
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