Capilliposide Isolated from Lysimachia capillipes Hemsl. Induces ROS Generation, Cell Cycle Arrest, and Apoptosis in Human Nonsmall Cell Lung Cancer Cell Lines
Several data has reported that capilliposide, extracted from a traditional Chinese medicine, Lysimachia capillipes Hemsl. (LC) could exhibit inhibitory effect on cell proliferation in various cancers. The current study investigated the antitumor efficacy of Capilliposide and elucidated its potential molecular mechanism involved in vivo and vitro. Our results indicated that LC capilliposide inhibited proliferation of lung cancer cells in a dose-dependent manner. LC capilliposide induced cell cycle arrest at the S stage and enhanced apoptosis in NSCLC cells. Treatment with LC capilliposide increased the intracellular level of ROS, which activated the mitochondrial apoptotic pathway. Blockage of ROS by NAC highly reversed the effect of LC capilliposide on apoptosis. Xenograft tumor growth was significantly lower in the LC-treated group compared with the untreated control group . The results also show that LC treatment does not produce any overt signs of acute toxicity in vivo. These findings demonstrate that LC capilliposide could exert an anti-tumor effect on NSCLC through mitochondrial-mediated apoptotic pathway and the activation of ROS is involved. 1. Introduction Lung cancer has been the most common malignant tumor worldwide and the leading cause of human cancer-related deaths for several decades [1]. Nonsmall cell lung cancer (NSCLC) accounts for nearly 80% of lung cancer cases and approximately two thirds of these patients are diagnosed at an advanced stage. Chemotherapy or radiation therapy is largely ineffective and highly toxic with a low survival profile. Although the prognosis is improved by early diagnosis and treatment, tumor recurrence and progression still plague some patients [2]. Developing novel drugs and therapies with fewer side effects is of significance for prognosis of patients with NSCLC [3]. Reactive oxygen species (ROS) including superoxide anion, hydroxyl radicals, and hydrogen peroxide (H2O2) are produced by all aerobic cells, which had important role in variety of various biological processes during physiological and pathological conditions [4]. ROS are thought to play multiple roles in tumorigenesis, progression, and maintenance [5]. On the one hand, cancerous cells have shown a higher level of ROS compared with their noncancerous counterparts. Up-regulation of ROS is usually accompanied with oncogene activation which may contribute to cancer progression. On the other hand, an imbalance between production of ROS and antioxidant depletion results in irreversible oxidative stress. Anticancer drugs and ionizing radiation may be
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