c-Jun N-terminal kinase-dependent apoptotic photocytotoxicity of solvent exchange-prepared curcumin nanoparticles

Biomed Microdevices. 2016 Apr;18(2):37. doi: 10.1007/s10544-016-0062-2.

Abstract

Indian spice curcumin is known for its anticancer properties, but the anticancer mechanisms of nanoparticulate curcumin have not been completely elucidated. We here investigated the in vitro anticancer effect of blue light (470 nm, 1 W)-irradiated curcumin nanoparticles prepared by tetrahydrofuran/water solvent exchange, using U251 glioma, B16 melanoma, and H460 lung cancer cells as targets. The size of curcumin nanocrystals was approximately 250 nm, while photoexcitation induced their oxidation and partial agglomeration. Although cell membrane in the absence of light was almost impermeable to curcumin nanoparticles, photoexcitation stimulated their internalization. While irradiation with blue light (1-8 min) or nanocurcumin (1.25-10 μg/ml) alone was only marginally toxic to tumor cells, photoexcited nanocurcumin displayed a significant cytotoxicity depending both on the irradiation time and nanocurcumin concentration. Photoexcited nanocurcumin induced phosphorylation of c-Jun N-terminal kinase (JNK), mitochondrial depolarization, caspase-3 activation, and cleavage of poly (ADP-ribose) polymerase, indicating apoptotic cell death. Accordingly, pharmacologial inhibition of JNK and caspase activity rescued cancer cells from photoexcited nanocurcumin. On the other hand, antioxidant treatment did not reduce photocytotoxicity of nanocurcumin, arguing against the involvement of oxidative stress. By demonstrating the ability of photoexcited nanocurcumin to induce oxidative-stress independent, JNK- and caspase-dependent apoptosis, our results support its further investigation in cancer therapy.

Keywords: Apoptosis; Cancer; JNK; Nanocurcumin; Photoexcitation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Biological Transport / radiation effects
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cell Membrane / radiation effects
  • Curcumin / chemistry*
  • Curcumin / metabolism
  • Curcumin / pharmacology*
  • Enzyme Activation / drug effects
  • Enzyme Activation / radiation effects
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Light*
  • Mice
  • Mitochondria / drug effects
  • Mitochondria / radiation effects
  • Nanoparticles / chemistry*
  • Oxidative Stress / drug effects
  • Oxidative Stress / radiation effects
  • Particle Size
  • Solvents / chemistry*

Substances

  • Antineoplastic Agents
  • Solvents
  • JNK Mitogen-Activated Protein Kinases
  • Caspase 3
  • Curcumin