Combined regimen of photodynamic therapy mediated by Gallium phthalocyanine chloride and Metformin enhances anti-melanoma efficacy.

Title Combined regimen of photodynamic therapy mediated by Gallium phthalocyanine chloride and Metformin enhances anti-melanoma efficacy.
Authors D. Tudor; I. Nenu; G.Adriana Filip; D. Olteanu; M. Cenariu; F. Tabaran; R.Mariana Ion; L. Gligor; I. Baldea
Journal PLoS One
DOI 10.1371/journal.pone.0173241
Abstract

BACKGROUND: Melanoma therapy is challenging, especially in advanced cases, due to multiple developed tumor defense mechanisms. Photodynamic therapy (PDT) might represent an adjuvant treatment, because of its bimodal action: tumor destruction and immune system awakening. In this study, a combination of PDT mediated by a metal substituted phthalocyanine-Gallium phthalocyanine chloride (GaPc) and Metformin was used against melanoma. The study aimed to: (1) find the anti-melanoma efficacy of GaPc-PDT, (2) assess possible beneficial effects of Metformin addition to PDT, (3) uncover some of the mechanisms underlining cell killing and anti-angiogenic effects.

METHODS: Two human lightly pigmented melanoma cell lines: WM35 and M1/15 subjected to previous Metformin exposure were treated by GaPc-PDT. Cell viability, death mechanism, cytoskeleton alterations, oxidative damage, were assessed by means of colorimetry, flowcytometry, confocal microscopy, spectrophotometry, ELISA, Western Blotting.

RESULTS: GaPc proved an efficient photosensitizer. Metformin addition enhanced cell killing by mechanisms dependent on the cell line, namely apoptosis in the metastatic M1/15 and necrosis in the radial growth phase, WM35. Cell death mechanism relied on the inhibition of nuclear transcription factor (NF)-?B activation and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) sensitization, leading to TRAIL and TNF-? induced apoptosis. Metformin diminished the anti-angiogenic effect of PDT.

CONCLUSIONS: Metformin addition to GaPc-PDT increased tumor cell killing through enhanced oxidative damage and induction of proapoptotic mechanisms, but altered PDT anti-angiogenic effects.

GENERAL SIGNIFICANCE: Combination of Metformin and PDT might represent a solution to enhance the efficacy, leading to a potential adjuvant role of PDT in melanoma therapy.

Citation D. Tudor; I. Nenu; G.Adriana Filip; D. Olteanu; M. Cenariu; F. Tabaran; R.Mariana Ion; L. Gligor; I. Baldea.Combined regimen of photodynamic therapy mediated by Gallium phthalocyanine chloride and Metformin enhances anti-melanoma efficacy.. PLoS ONE. 2017;12(3):e0173241. doi:10.1371/journal.pone.0173241

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See more Gallium products. Gallium (atomic symbol: Ga, atomic number: 31) is a Block P, Group 13, Period 4 element with an atomic weight of 69.723.The number of electrons in each of Gallium's shells is 2, 8, 18, 3 and its electron configuration is [Ar] 3d10 4s2 4p1. The gallium atom has a radius of 122.1 pm and a Van der Waals radius of 187 pm. Gallium Bohr ModelGallium was predicted by Dmitri Mendeleev in 1871. It was first discovered and isolated by Lecoq de Boisbaudran in 1875. In its elemental form, gallium has a silvery appearance. Elemental GalliumGallium is one of three elements that occur naturally as a liquid at room temperature, the other two being mercury and cesium. Gallium does not exist as a free element in nature and is sourced commercially from bauxite and sphalerite. Currently, gallium is used in semiconductor devices for microelectronics and optics. The element name originates from the Latin word 'Gallia' referring to Gaul, the old name of France.

Chlorine

Chlorine is a Block P, Group 17, Period 3 element. Its electron configuration is [Ne]3s23p5. The chlorine atom has a covalent radius of 102±4 pm and its Van der Waals radius is 175 pm. Chlorine ModelIn its elemental form, chlorine is a yellow-green gas. Chlorine is the second lightest halogen after fluorine. It has the third highest electronegativity and the highest electron affinity of all elements, making it a strong oxidizing agent. It is rarely found by itself in nature. Chlorine was discovered and first isolated by Carl Wilhelm Scheele in 1774. It was first recognized as an element by Humphry Davy in 1808.

Nitrogen

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