title: Differentiation-inducing activity of hydroxycamptothecin on cancer stem-like cells derived from hepatocellular carcinoma.
abstract: BACKGROUND
  Hydroxycamptothecin (HCPT) is an anti-tumor agent that can induce differentiation in human cancer cells. Recent evidence indicates that side population (SP) cells possess characteristics of stem-like cells, and may be capable of initiating tumor growth.
  
  
  OBJECTIVE
  The present study investigated the differentiation of cancer stem-like cells derived from hepatocellular carcinoma.
  
  
  RESULTS
  Flow cytometry was used to isolated SP cells from HCC cell line (MHCC97 cells). These SP cells exhibit several stem-like cell characteristics that are distinct from the main population (MP) cells in vitro. After 3 days of induction with a low concentration of HCPT, the SP cells lost their capacity to proliferate and invade, and their tumorigenicity declined. Based on real-time quantitative RT-PCR, we also found that the expression of hepatocyte-specific markers such as α-fetoprotein, albumin, hepatocyte nuclear factor-4 and miR-122 gradually changed during the differentiation of SP cells.
  
  
  CONCLUSIONS
  Our data suggest that a low concentration of HCPT can induce hepatocyte-specific differentiation of cancer stem-like cells from MHCC97 cells, offering a possible therapeutic strategy for the treatment of human malignancies.
authors.affiliation: Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, 17 Changlexi Road, Xi'an, Shaanxi Province, 710032, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Song
authors.forename: Fu-Qin
authors.initials: FQ
authors.lastname: Zhang
authors.forename: Wei-Hui
authors.initials: WH
authors.lastname: Liu
authors.forename: Ke-Feng
authors.initials: KF
authors.lastname: Dou
mesh_terms: D000418:Albumins / Q000096:biosynthesis; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D051557:Hepatocyte Nuclear Factor 4 / Q000096:biosynthesis; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D035683:MicroRNAs / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology*; D058985:Side-Population Cells / Q000187:drug effects*; D000509:alpha-Fetoproteins / Q000096:biosynthesis
chemical_list: D000418:Albumins; D000972:Antineoplastic Agents, Phytogenic; D051557:Hepatocyte Nuclear Factor 4; C531907:MIRN122 microRNA, human; D035683:MicroRNAs; D000509:alpha-Fetoproteins; C527042:hydroxycamptothecinum; D002166:Camptothecin