title: Holotransferrin enhances selective anticancer activity of artemisinin against human hepatocellular carcinoma cells.
abstract: Artemisinin, also termed qinghaosu, is extracted from the traditional Chinese medicine artemesia annua L. (the blue-green herb) in the early 1970s, which has been confirmed for effectively treating malaria. Additionally, emerging data prove that artemisinin exhibits anti-cancer effects against many types of cancers such as leukemia, melanoma, etc. Artemisinin becomes cytotoxic in the presence of ferrous iron. Since iron influx is high in cancer cells, artemisinin and its analogs selectively kill cancer cells with increased intracellular iron concentrations. This study is aimed to investigate the selective inhibitory effects of artemisinin on SMMC-7721 cells in vitro and determine the effect of holotransferrin, which increases the concentration of ferrous iron in cancer cells, combined with artemisinin on the anticancer activity. MTT assay was used for assessing the proliferation of SMMC-7721 cells treated with artemisinin. The induction of apoptosis and inhibition of colony formation in SMMC-7721 cells treated with artemisinin were determined by TdT-mediated dUTP nick end labeling (TUNEL) and colony formation assay, respectively. The results showed that artemisinin at various concentrations significantly inhibited growth, colony formation and cell viability of SMMC-7721 cells (P<0.05), likely due to induction of apoptosis of SMMC-7721 cells. Of interest, it was found that incubation of artemisinin combined with holotransferrin sensitized the growth inhibitory effect of artemisinin on SMMC-7721 cells (P<0.01). Our data suggest that treatment with artemisinin leads to inhibition of viability and proliferation, and apoptosis of SMMC-7721 cells. Furthermore, we observed that holotransferrin significantly enhanced the anti-cancer activity of artemisinin. This study may provide a potential therapeutic choice for liver cancer.
authors: Department of General Surgery, Nanshan Affiliated Hospital of Guangdong Medical College, Shenzhen, 518052, China. dengxr77@163.com.
authors: Xiao-Rong
authors: XR
authors: Deng
authors: Department of Obstetrics and Gynecology, Nanshan Affiliated Hospital of Guangdong Medical College, Shenzhen, 518052, China.
authors: Zhao-Xia
authors: ZX
authors: Liu
authors: Department of General Surgery, First Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
authors: Feng
authors: F
authors: Liu
authors: Department of General Surgery, Qihe People's Hospital, Qihe, 251100, China.
authors: Lei
authors: L
authors: Pan
authors: Department of General Surgery, Wuhan Pu'ai Hospital, Wuhan, 430033, China. yuheping12@163.com.
authors: He-Ping
authors: HP
authors: Yu
authors: Department of General Surgery, First Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
authors: Jin-Ping
authors: JP
authors: Jiang
authors: Department of General Surgery, Nanshan Affiliated Hospital of Guangdong Medical College, Shenzhen, 518052, China.
authors: Jian-Jun
authors: JJ
authors: Zhang
authors: Department of General Surgery, Nanshan Affiliated Hospital of Guangdong Medical College, Shenzhen, 518052, China.
authors: Li
authors: L
authors: Liu
authors: Department of General Surgery, Nanshan Affiliated Hospital of Guangdong Medical College, Shenzhen, 518052, China.
authors: Jun
authors: J
authors: Yu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D037621:Artemisinins / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D045744:Cell Line, Tumor; D004357:Drug Synergism; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism; D014168:Transferrin / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D037621:Artemisinins; D014168:Transferrin; C110714:holotransferrin; C031327:artemisinin