| Summary: | 碩士 === 嘉南藥理科技大學 === 營養與保健科技研究所 === 99 === Non-small cell lung cancer (NSCLC) comprises over approximately 75% in all lung cancers. Despite development of medicine have rapid advances in pharmacology, the treatment of NSCLC patients remain extremely insufficient at terminal care. Therefore an effective therapy for treatment of patients with NSCLC is urgently needed. KOH-AL1, a natural lignan isolated from leaves of Koelreuteria henryi Dummer, has antioxidant, and anitproliferative activities. However, the effects of KOH-AL1 on NSCLC cells have not been studied. This study was aimed to examine the effects and underlying mechanisms of KOH-AL1 in regulating cell growth and survival in human lung adenocarcinoma A549 cells. Treatment of A549 cells with KOH-AL1 resulted in inhibiting cell proliferation and arresting cell cycle at G2/M phase. Data from immunoblot analysis showed that the protein levels of cyclin A and CDC25C were decreased, but p53, p27KIP 1, p21CIP/WAF 1 and cyclin B1 were increased that might contribute to KOH-AL1-induced cell cycle G2/M phase perturbation. In addition, KOH-AL1 also induced apoptosis in A549 cells which was characterized by TUNEL assay, the TUNEL positive cells were remarkably increased upon KOH-AL1 treatment. Moreover, exposure to KOH-AL1 could increase the levels of p53 and phosphorylated p53ser15, phosphorylated DNA-PKCS, phosphorylated ATM, phosphorylated ERK and phosphorylated JNK, as well as pro-apoptotic proteins including Bax and Bak. However, the levels of anti-apoptotic proteins such as Mcl-1, Bcl-2 and the phosphorylated AKTser473 were significantly decreased after incubation with KOH-AL1. Furthermore, KOH-AL1 treatment caused cytochrome c releasing from mitochondria to cytoplasm, activation of caspase-2, caspase-9 and caspase-3, preceding morphologic features of apoptosis. Taken together, KOH-AL1 was capable of eliciting cell cycle G2/M-phase arrest and inducing intrinsic apoptotic cell death in human lung adenocarcinoma A549 cells. This study provides a molecular basis for evaluation of the potential therapeutic use of KOH-AL1 in NSCLC treatment.
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