Pathway of programmed cell death in HeLa cells induced by polymeric anti-cancer drugs

Biomaterials. 2011 May;32(14):3637-46. doi: 10.1016/j.biomaterials.2011.01.060. Epub 2011 Feb 12.

Abstract

Synthesis of anticancer polymeric materials plus their biological applications is one of the most charming and active research areas in biological functional materials. However, the predominant mechanisms for controlling cancer cell viability are not yet clear. In this work, cell culture polymeric materials co-immobilized with death signal proteins interferon-γ (IFN-γ)/tumor necrosis factor-α (TNF-α) on the surface were prepared by photochemical method to develop an anticancer polymeric drug model. Various characterizations on the microstructures and compositions, including the Fourier transform infrared spectroscopy, UV absorption spectroscopy, fluorescence measurement, atomic force microscopy, and electron spectroscopy for chemical analysis, were performed. For addressing the biological applications, we investigated systematically the death pathways of HeLa cells attached onto the drug model by means of a series of cell-biology techniques. It was demonstrated that the IFN-γ plus TNF-α co-immobilized on the polymeric material surface exhibited more notable inhibitive effects than the free IFN-γ plus TNF-α, and the induced HeLa cells were mainly along apoptosis-like PCD with the translocation of EndoG from the cytoplasm to the nucleus. These findings indicate that the polymeric drugs with the co-immobilized IFN-γ plus TNF-α may offer significant potentials for therapeutic manipulation of human cervical cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Blotting, Western
  • Cell Survival / drug effects
  • Fluorescent Antibody Technique
  • HeLa Cells
  • Humans
  • Immunohistochemistry
  • Interferon-gamma / chemistry
  • Interferon-gamma / pharmacology*
  • Polymerase Chain Reaction
  • Polymers / chemistry*
  • Tumor Necrosis Factor-alpha / chemistry
  • Tumor Necrosis Factor-alpha / pharmacology*

Substances

  • Antineoplastic Agents
  • Polymers
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma