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Lijun Zhang,1,* Jun Liang,1,* Xiaohua Liu,1 Jianhua Wu,1 Daqing Tan,1 Wei Hu2 1Department of Urology, Minda Hospital Affiliated to Hubei Minzu University, Enshi, Hubei Province, People’s Republic of China; 2Department of Urology, The First Affiliated Hospital of University of South of China, Hengyang, Hunan Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lijun Zhang Tel +8615171021486Email zlj05052@163.comBackground: Human bladder cancer is the most common malignant tumor of the urinary system and one of the 10 most common tumors of the whole body. Although most patients with bladder cancer exhibit a good prognosis with standard treatment, effective therapies for patients with a recurrent or advanced bladder cancer are unavailable. Therefore, highly effective drugs to treat such patients need to be developed. Aloperine (ALO), a natural compound isolated from Sophora alopecuroides, has antitumor properties. However, the role of ALO in human bladder cancer remains unclear.Methods: In the present study, MTT was used to detect the cytotoxic effect of ALO on human BC cell line EJ and human urotheliumcell line SV-HUC-1cells. Meanwhile, in order to investigate the effects of ALO on the proliferation, apoptosis, migration, and invasion of BC EJ cells and its mechanism by Cell Counting Kit-8 (CCK-8) assay, immunofluorescence, Hoechst 33342 staining, wound scratch assay, transwell migration and invasion assay, Western blot analysis.Results: ALO can inhibit the proliferation and invasion of human bladder cancer EJ cells, and is low-toxic to human urothelium cells. Moreover, it can promote cellular apoptosis in vitro. Further analysis demonstrated the involvement of Caspase-dependent apoptosis following ALO treatment. ALO also downregulated the protein expression levels of Ras, p-Raf1 and p-Erk1/2.Conclusion: ALO is a potential drug for human bladder cancer therapy.Keywords: Aloperine, bladder cancer, apoptosis

Zhixin Ling,1,2,* Han Guan,3,* Zonghao You,1,2,* Can Wang,1,2 Ling Hu,4 Lei Zhang,1,2 Yiduo Wang,1,2 Shuqiu Chen,1,2 Bin Xu,1,2 Ming Chen1,2 1Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, People’s Republic of China; 2Surgical Research Center, Institute of Urology, Medical School of Southeast University, Nanjing, People’s Republic of China; 3Department of Urology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, People’s Republic of China; 4Department of Nephrology, People’s Hospital of Wuxi City, Wuxi, People’s Republic of China *These authors contributed equally to this work Background: Prostate cancer (PCa) is one of the most common malignant diseases among male patients. Although androgen deprivation therapy remains the main treatment for PCa, most patients would inevitably progress to castration-resistant PCa, which is the main cause of cancer-related deaths. Thus, novel antitumor agents are urgently needed. Recent studies demonstrated that aloperine (ALO) as a natural alkaloid showed antitumor effects in other cancer types. However, the biological function and underlying mechanisms of ALO in PCa have not been investigated. Methods: PCa cell lines including LNCaP, PC3 and DU145 were cultured and treated with ALO. Cell Counting Kit-8 assay, colony formation assay, apoptosis assay and cell cycle assay were conducted to assess the biological role of ALO. In addition, a PCa subcutaneous xenograft mouse model was established to evaluate the role of ALO in terms of proliferation and apoptosis in vivo. We further measured the protein expression levels of p-Akt/Akt, p-ERK/ERK, c-Myc, cleaved caspase 3, p21, p53, Bcl-2 and Bax using the Western blot 48 h after ALO treatment of PCa cells. Results: ALO effectively inhibited the cell viability of PCa by inducing cell cycle arrest via the activation of the p53/p21 pathway and triggering apoptosis in vitro and in vivo. ALO also inhibited phosphorylation of Akt and ERK protein kinases and activated cleaved caspase 3 while exerting antiproliferation function through inducing apoptosis and cell cycle arrest in PCa cells. Conclusion: Based on our findings, we conclude that ALO could suppress the tumor growth and promote cell apoptosis and cell cycle arrest in PCa cells, which indicated that ALO could act as a novel therapeutic agent in treatment of human PCa. Keywords: aloperine, prostate cancer, proliferation, apoptosis, cell cycle