Killing efficacy of a new silicon phthalocyanine in human melanoma cells treated with photodynamic therapy by early activation of mitochondrion‐mediated apoptosis

Abstract

Photodynamic therapy (PDT) is a promising therapeutic modality that utilizes a combination of a photosensitizer and visible light for the destruction of diseased tissues. Using human-pigmented melanoma cells, we examined the photokilling efficacy of new silicon-phthalocyanines (SiPc) that bore bulky axial substituents. The bis(cholesteryloxy) derivate (Chol-O-SiPc) displayed the best in vitro photokilling efficacy (LD(50) = 6-8 x 10(-9) M) and was seven to nine times more potent than chloro-aluminium Pc (ClAlPc), a known photosensitizer used as a reference. Although Chol-O-SiPc was half as potent as ClAlPc for promoting photo-oxidative membrane damage in a cell-free assay, early events of mitochondrion-mediated apoptosis upon PDT were triggered much faster, as demonstrated by kinetics studies examining cells with permeabilized mitochondrial membranes, cytochrome c release and caspase-9 activation. Inhibition of caspase-9 activity by a substrate analogue argued for its central role in the proapoptotic events leading to cell death by Chol-O-SiPc PDT. In addition, immunoblots showed that Bcl-2 antiapoptotic oncoprotein was not a primary target of Chol-O-SiPc in M3Dau cells treated with PDT. Conclusively, Chol-O-SiPc is a useful new photosensitizer with the property of triggering cell apoptosis mediated by mitochondria.

Photodynamic therapy effect of zinc monoamino phthalocyanine–folic acid conjugate adsorbed on single walled carbon nanotubes on melanoma cells

“…As stated above, folic acid also imparts water solubility in phthalocyanines [9], making cell studies easier. There have been studies where MPc were used in the treatment of melanoma cell [10][11][12]. We are reporting for the first time the effect of MPc linked to folic acid on melanoma cell line.…”

Current position of TNF-α in melanomagenesis

“…PDT unveils encouraging results on in vitro and in vivo experimental models, as well as few clinical reports, suggesting a possible role in the management of advanced melanoma [108][109][110][111]. PDT is an ideal theoretical approach because it induces direct tumor cell photodamage, targets tumor vasculature, and activates the immune response.…”

Steroid-photosensitizer conjugates: Syntheses and applications

“…Immunoblots showed that Bcl-2 anti-apoptotic-onco-protein was not a primary target of Chol-O-SiPc in M3Dau cells treated by PDT. The authors concluded that the capacity of 125b to induce cell apoptosis via mitochondrial damage renders the complex of interest as a PS for PDT [94].…”