Nanoliposomal ceramide prevents in vivo growth of hepatocellular carcinoma.

Academic Article

Abstract

  • BACKGROUND AND OBJECTIVES: Hepatocellular carcinoma (HCC) affects an increasing number of people worldwide. The poor survival rate of patients with HCC is manifested by an aggressive and metastatic phenotype, as well as a poor response to common therapeutic strategies. The purpose of this study was to evaluate the efficacy of nanoliposomal C6-ceramide as an antineoplastic agent in an in vivo model of human HCC. METHODS: The growth-arresting and pro-apoptotic properties of nanoliposomal C6-ceramide were first evaluated in vitro in human SK-HEP-1 cells by assessing cellular viability, caspase 3/7 activity, annexin-V expression, DNA fragmentation, cell cycle distribution and AKT phosphorylation. SK-HEP-1 cells were then engrafted subcutaneously into athymic nude mice and nanoliposomal C6-ceramide was administered by tail vein injection. Tumour size was monitored over time, followed by excision of tumours to evaluate tumour vascularisation, proliferation, apoptosis and cellular signalling. RESULTS: Nanoliposomal C6-ceramide, but not ghost (no ceramide) nanoliposomes, induced apoptotic cell death of SK-HEP-1 cells in vitro, concomitant with an accumulation of cells in the G₂ phase of the cell cycle and decreased phosphorylation of AKT. Systemic administration of nanoliposomal C6-ceramide to mice engrafted with SK-HEP-1 tumours reduced tumour vascularisation and proliferation, induced tumour cell apoptosis, decreased phosphorylation of AKT and ultimately blocked tumour growth. CONCLUSIONS: These studies show that nanoliposomal ceramide is an efficacious antineoplastic agent for the treatment of in vitro and in vivo models of human HCC.
  • Authors

  • Tagaram, Hephzibah Rani S
  • Divittore, Nicole A
  • Barth, Brian
  • Kaiser, James M
  • Avella, Diego
  • Kimchi, Eric T
  • Jiang, Yixing
  • Isom, Harriet C
  • Kester, Mark
  • Staveley-O'Carroll, Kevin F
  • Status

    Publication Date

  • May 2011
  • Published In

  • Gut  Journal
  • Keywords

  • Animals
  • Antineoplastic Agents
  • Apoptosis
  • Carcinoma, Hepatocellular
  • Cell Cycle
  • Ceramides
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Liposomes
  • Liver Neoplasms
  • Liver Neoplasms, Experimental
  • Mice
  • Mice, Nude
  • Nanoparticles
  • Neovascularization, Pathologic
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays
  • Digital Object Identifier (doi)

    Pubmed Id

  • 21193455
  • Start Page

  • 695
  • End Page

  • 701
  • Volume

  • 60
  • Issue

  • 5