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

Biomedical Microdevices volume 18, Article number: 37 (2016) Cite this article

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.

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Acknowledgments

The study was supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia (grants 41025 to VT, 172003 to BTM, and 173053 to LHT), by the SASPRO Program project 1237/02/02-b and the People Program (Marie Curie Actions) European Union’s Seventh Framework Program under REA grant agreement No. 609427 (grant to ZM). Research has been further co-funded by the Slovak Academy of Sciences (grant to ZS).

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Affiliations

  1. Institute of Microbiology and Immunology, School of Medicine, University of Belgrade, Dr Subotica 1, Belgrade, 11000, Serbia

    Verica Paunovic, Biljana Ristic, Milica Kosic & Vladimir Trajkovic

  2. Polymer Institute, Slovak Academy of Sciences, Dubravska cesta 9, 84541, Bratislava, Slovakia

    Zoran Markovic, Matej Micusik & Zdeno Spitalsky

  3. Vinca Institute of Nuclear Sciences, University of Belgrade, P.O. Box 522, Mike Petrovica Alasa 12-14, Belgrade, 11001, Serbia

    Biljana Todorovic-Markovic & Jovana Prekodravac

  4. Institute of Histology and Embryology, School of Medicine, University of Belgrade, Visegradska 26, Belgrade, 11000, Serbia

    Tamara Kravic-Stevovic & Tamara Martinovic

  5. Institute for Biological Research “Sinisa Stankovic”, University of Belgrade, Despot Stefan Blvd. 142, Belgrade, 11000, Serbia

    Ljubica Harhaji-Trajkovic

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  1. Verica Paunovic
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Correspondence to Ljubica Harhaji-Trajkovic.

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Paunovic, V., Ristic, B., Markovic, Z. et al. c-Jun N-terminal kinase-dependent apoptotic photocytotoxicity of solvent exchange-prepared curcumin nanoparticles. Biomed Microdevices 18, 37 (2016). https://doi.org/10.1007/s10544-016-0062-2

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Keywords

  • Nanocurcumin
  • Photoexcitation
  • Cancer
  • Apoptosis
  • JNK