c-Jun N-terminal kinase-dependent apoptotic photocytotoxicity of solvent exchange-prepared curcumin nanoparticles.
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.
Institute of Microbiology and Immunology, School of Medicine, University of Belgrade, Dr Subotica 1, Belgrade, 11000, Serbia.
Verica
V
Paunovic
Institute of Microbiology and Immunology, School of Medicine, University of Belgrade, Dr Subotica 1, Belgrade, 11000, Serbia.
Biljana
B
Ristic
Polymer Institute, Slovak Academy of Sciences, Dubravska cesta 9, 84541, Bratislava, Slovakia.
Zoran
Z
Markovic
Vinca Institute of Nuclear Sciences, University of Belgrade, P.O. Box 522, Mike Petrovica Alasa 12-14, Belgrade, 11001, Serbia.
Biljana
B
Todorovic-Markovic
Institute of Microbiology and Immunology, School of Medicine, University of Belgrade, Dr Subotica 1, Belgrade, 11000, Serbia.
Milica
M
Kosic
Vinca Institute of Nuclear Sciences, University of Belgrade, P.O. Box 522, Mike Petrovica Alasa 12-14, Belgrade, 11001, Serbia.
Jovana
J
Prekodravac
Institute of Histology and Embryology, School of Medicine, University of Belgrade, Visegradska 26, Belgrade, 11000, Serbia.
Tamara
T
Kravic-Stevovic
Institute of Histology and Embryology, School of Medicine, University of Belgrade, Visegradska 26, Belgrade, 11000, Serbia.
Tamara
T
Martinovic
Polymer Institute, Slovak Academy of Sciences, Dubravska cesta 9, 84541, Bratislava, Slovakia.
Matej
M
Micusik
Polymer Institute, Slovak Academy of Sciences, Dubravska cesta 9, 84541, Bratislava, Slovakia.
Zdeno
Z
Spitalsky
Institute of Microbiology and Immunology, School of Medicine, University of Belgrade, Dr Subotica 1, Belgrade, 11000, Serbia.
Vladimir
V
Trajkovic
Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Despot Stefan Blvd. 142, Belgrade, 11000, Serbia. buajk@yahoo.com.
Ljubica
L
Harhaji-Trajkovic
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001692:Biological Transport / Q000528:radiation effects; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D003474:Curcumin / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008027:Light; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000528:radiation effects; D053758:Nanoparticles / Q000737:chemistry*; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects; D010316:Particle Size; D012997:Solvents / Q000737:chemistry*
D000970:Antineoplastic Agents; D012997:Solvents; D048031:JNK Mitogen-Activated Protein Kinases; D053148:Caspase 3; D003474:Curcumin
Apoptosis; Cancer; JNK; Nanocurcumin; Photoexcitation