Differentiation-inducing activity of hydroxycamptothecin on cancer stem-like cells derived from hepatocellular carcinoma

Dig Dis Sci. 2011 Aug;56(8):2473-81. doi: 10.1007/s10620-011-1601-6. Epub 2011 Feb 12.

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.

Aims: The present study investigated the differentiation of cancer stem-like cells derived from hepatocellular carcinoma.

Methods and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albumins / biosynthesis
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Camptothecin / analogs & derivatives*
  • Camptothecin / pharmacology
  • Carcinoma, Hepatocellular / pathology*
  • Cell Differentiation / drug effects*
  • Cell Line, Tumor
  • Flow Cytometry
  • Hepatocyte Nuclear Factor 4 / biosynthesis
  • Humans
  • Liver Neoplasms / pathology*
  • MicroRNAs / metabolism
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / pathology*
  • Side-Population Cells / drug effects*
  • alpha-Fetoproteins / biosynthesis

Substances

  • Albumins
  • Antineoplastic Agents, Phytogenic
  • Hepatocyte Nuclear Factor 4
  • MIRN122 microRNA, human
  • MicroRNAs
  • alpha-Fetoproteins
  • hydroxycamptothecinum
  • Camptothecin