Isocorydine Targets the Drug-Resistant Cellular Side Population through PDCD4-Related Apoptosis in Hepatocellular Carcinoma |
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| Authors: | Ping Lu Hefen Sun Lixing Zhang Helei Hou Lin Zhang Fangyu Zhao Chao Ge Ming Yao Tingpu Wang Jinjun Li |
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| Institution: | 1.Shanghai Medical College, Fudan University, Shanghai, China;2.State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Jiaotong University School of Medicine, Shanghai, China;3.Experimental Pathological Laboratory, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China;4.College of Life Sciences and Chemistry, Tianshui Normal University, Tianshui, China |
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| Abstract: | Isocorydine (ICD), an anticancer agent under current evaluation, decreased the percentage of side population (SP) cells significantly in hepatocellular carcinoma (HCC) cell lines. ICD treatment sensitized cancer cells to doxorubicin (DXR), a conventional clinical chemotherapeutic drug for HCC. We found that ICD decreased the percentage of SP cells in HCC cell lines by preferentially killing SP cells. In the early stage of treatment, ICD inhibited SP cell growth by arresting cells in G2/M; later, it induced apoptosis. Our xenograft model confirmed that ICD selectively reduced the size and weight of SP-induced tumor masses in vivo. Furthermore, it was found that programmed cell death 4 (PDCD4), a tumor suppressor gene, was relatively low when expressed in SP cells compared with non-SP cells, and its expression level was remarkably elevated when cells were treated with ICD. Taken together, these data suggest that ICD is a drug that may target the SP cells of HCC. |
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