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Usnic Acid Induces Cycle Arrest, Apoptosis, and Autophagy in Gastric Cancer Cells In Vitro and In Vivo

Xiaoge Geng, Xing Zhang, Bin Zhou, Chenjing Zhang, Jiangfeng Tu, Xiaojun Chen, Jingya Wang, Huiqin Gao, Guangming Qin, Wensheng Pan

(Department of Gastroenterology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China (mainland))

Med Sci Monit 2018; 24:556-566

DOI: 10.12659/MSM.908568

BACKGROUND: Usnic acid (UA), a secondary metabolite, is mainly derived from certain lichen species. Growing evidence suggests that UA has antitumor, anti-oxidative, anti-inflammatory, and other activities in a variety of cancer cells. However, the antitumor effect of UA in gastric cancer cells (GC) is unclear. The aim of this investigation was to assess the antitumor effect of UA in GC cells in vitro and in vivo, and to explore the underlying mechanisms.
MATERIAL AND METHODS: Cell proliferation was measured by CCK8 assay, the arrest of cell cycle was assessed by flow cytometry, and cellular apoptosis was observed via Hoechst 33258 staining assay. Expression levels of apoptosis-related proteins (activated caspase-3 and PARP, Bax, Bcl2) and autophagy-associated proteins (LC3-II and p62) were verified through Western blot analysis. H&E staining and immunohistochemistry were carried out in the subcutaneously implanted BGC823 tumor model in a nude mouse experiment.
RESULTS: In vitro, we demonstrated that UA was significantly effective in inducing morphological changes, inhibiting the cell proliferation dose- and time-dependently, arresting the cell cycle phase, promoting cancer cellular apoptosis, and inducing autophagy activity. In vivo, compared to mice treated with 5-FU alone, UA treatment was significantly more effective in suppressing the tumor growth without affecting body weight, and in regulating the amount of Bax and Bcl2 in tumor tissues.
CONCLUSIONS: UA induces cell cycle arrest and autophagy and exerts anti-proliferative and apoptotic effects by modulating expression of apoptosis-related proteins in stomach neoplasm cells, and has a better antitumor effect compared to 5-Fu in the xenograft model.

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