Berberine as a photosensitizing agent for antitumoral photodynamic therapy: Insights into its association to low density lipoproteins.
Recent years have seen a growing interest in Berberine, a phytochemical with multispectrum therapeutic activities, as anti-tumoral agent for photodynamic therapy (PDT). In this context, low density lipoproteins (LDL) play a key role in the delivery of the photosensitizer in tumor cells. We correlate the physicochemical parameters of the berberine association to LDL with the influence of LDL-delivery on its accumulation in a glioma cell line and on its photo-induced activity in view of antitumor PDT. Our results evidence an important binding of 400 berberine molecules per LDL. Changes in berberine and apoprotein fluorescence suggest different fixation types, involving various LDL compartments including the vicinity of the apoprotein. The berberine association to LDL does not affect their recognition by the specific B/E receptors, of which over-expression increases the cellular uptake of LDL-preloaded berberine. Fluorescence microscopy evidences the mitochondrial labeling of the glioma model cells, with no significant modification upon LDL-delivery. Moreover, the cellular delivery of berberine by LDL increases its photocytotoxic effects on such cells. So, this research illustrates the potential of berberine as a photosensitizing agent for PDT, in particular due to their behavior towards LDL as plasma vehicles, and gives insights into its mechanisms of cell uptake.
Instituto de Biologia, Departamento de Biologia Vegetal, Universidade Estadual de Campinas (UNICAMP), 13083-970 Campinas, SP, Brazil. Electronic address: nathilu@gmail.com.
Nathalia
N
Luiza Andreazza
Sorbonne Universités, UPMC Univ Paris 06, Centre National de la Recherche Scientifique (CNRS), Laboratoire Jean Perrin (UMR 8237), 4 place Jussieu, 75252 Paris cedex 05, France.
Christine
C
Vevert-Bizet
Sorbonne Universités, UPMC Univ Paris 06, Centre National de la Recherche Scientifique (CNRS), Laboratoire Jean Perrin (UMR 8237), 4 place Jussieu, 75252 Paris cedex 05, France.
Geneviève
G
Bourg-Heckly
Sorbonne Universités, UPMC Univ Paris 06, Centre National de la Recherche Scientifique (CNRS), Laboratoire Jean Perrin (UMR 8237), 4 place Jussieu, 75252 Paris cedex 05, France.
Franck
F
Sureau
Instituto de Biologia, Departamento de Biologia Vegetal, Universidade Estadual de Campinas (UNICAMP), 13083-970 Campinas, SP, Brazil.
Marcos
M
José Salvador
Sorbonne Universités, UPMC Univ Paris 06, Centre National de la Recherche Scientifique (CNRS), Laboratoire Jean Perrin (UMR 8237), 4 place Jussieu, 75252 Paris cedex 05, France. Electronic address: stephanie.bonneau@upmc.fr.
Stephanie
S
Bonneau
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000378:metabolism*; D001599:Berberine / Q000008:administration & dosage / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D010775:Photic Stimulation / Q000379:methods; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000378:metabolism*
D000970:Antineoplastic Agents; D008077:Lipoproteins, LDL; D017319:Photosensitizing Agents; D001599:Berberine
Antitumor PDT; Berberine; Cellular uptake; Low-density lipoprotein; Subcellular localization