Holotransferrin enhances selective anticancer activity of artemisinin against human hepatocellular carcinoma cells

  • Xiao-rong Deng (邓小荣)
  • Zhao-xia Liu (刘朝霞)
  • Feng Liu (刘 峰)
  • Lei Pan (潘 雷)
  • He-ping Yu (余和平)
  • Jin-ping Jiang (姜进平)
  • Jian-jun Zhang (张建军)
  • Li Liu (刘 立)
  • Jun Yu (喻 军)


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.

Key words

human hepatocellular carcinoma SMMC-7721 cells artemisinin holotransferrin cell growth colony formation apoptosis 


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Copyright information

© Huazhong University of Science and Technology and Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Xiao-rong Deng (邓小荣)
    • 1
  • Zhao-xia Liu (刘朝霞)
    • 2
  • Feng Liu (刘 峰)
    • 3
  • Lei Pan (潘 雷)
    • 4
  • He-ping Yu (余和平)
    • 5
  • Jin-ping Jiang (姜进平)
    • 3
  • Jian-jun Zhang (张建军)
    • 1
  • Li Liu (刘 立)
    • 1
  • Jun Yu (喻 军)
    • 1
  1. 1.Department of General SurgeryNanshan Affiliated Hospital of Guangdong Medical CollegeShenzhenChina
  2. 2.Department of Obstetrics and GynecologyNanshan Affiliated Hospital of Guangdong Medical CollegeShenzhenChina
  3. 3.Department of General SurgeryFirst Affiliated Hospital of Nanchang UniversityNanchangChina
  4. 4.Department of General SurgeryQihe People’s HospitalQiheChina
  5. 5.Department of General SurgeryWuhan Pu’ai HospitalWuhanChina

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