title: Photodynamic efficiency of hypericin compared with chlorin and hematoporphyrin derivatives in HEp-2 and Vero epithelial cell lines.
abstract: Hypericin (HY) is a photoactive aromatic dianthraquinone that is considered a potent photodynamic agent. In this study, hypericin and two other photosensitizers, a hematoporphyrin derivative (Photogem(®); PG) and a chlorin derivative (Photodithazine(®); PZ), were compared in terms of their phototoxicity toward two cell lines, HEp-2 and Vero. The median inhibitory concentration (IC(50)) of each of the photosensitizers was obtained after a 16.2J cm(-2) dose of irradiation at 630 ± 10 nm. The IC(50) values were 0.07 ± 0.01 (HY), 1.0 ± 0.2 (PZ), and 9 ± 1 μgmL(-1) (PG) in HEp-2 cells and 0.3 ± 0.1 (HY), 1.6 ± 0.2 (PZ) and 11 ± 1 μgmL(-1) (PG) in Vero cells, showing that HY is more phototoxic than the others when irradiated at 630 nm. If these results are analyzed, simultaneously, with the first-order constant for BSA tryptophan photooxidation, obtained by fluorescence decay (λ(excitation)=280 nm), which are 11×10(-3) min(-1)±1. 10(-3) min(-1) (HY), 10 × 10(-3) min(-1)±1 × 10(-3) min(-1) (PZ), and 6 × 10(-3)min(-1) ± 1×10(-3)min(-1) (PG), it is possible to infer that the photodynamic efficiency alone is not sufficient to explain the higher HY phototoxicity. The lipophilicity is also an important factor for an efficient target cell accumulation and was assessed for all sensitizers through the octanol-water partition coefficient (log P): 1.20 ± 0.02 (HY), -0.62 ± 0.03 (PZ), and -0.9 ± 0.2 (PG). The higher value for HY correlates well with its observed superior efficiency to promote damage at low concentrations and doses. As HY is used for the long-term treatment of mild depression, it is considered safe for humans. This fact and the present results reinforce the great potential of this photosensitizer to replace porphyrin derivatives, with the advantages that mean it could be used as photosensitizer in clinical photodynamic therapy.
authors.affiliation: Instituto de Química de São Carlos, Universidade de São Paulo, São Carlos, SP, Brazil.
authors.forename: Claudia
authors.initials: C
authors.lastname: Bernal
authors.affiliation: Centro Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, SP, Brazil.
authors.forename: Anderson O
authors.initials: AO
authors.lastname: Ribeiro
authors.affiliation: Centro Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, SP, Brazil.
authors.forename: Gislaine P
authors.initials: GP
authors.lastname: Andrade
authors.affiliation: Instituto de Química de São Carlos, Universidade de São Paulo, São Carlos, SP, Brazil. Electronic address: janice@iqsc.usp.br.
authors.forename: Janice R
authors.initials: JR
authors.lastname: Perussi
mesh_terms: D000818:Animals; D000873:Anthracenes; D002460:Cell Line; D002470:Cell Survival; D002522:Chlorocebus aethiops; D005453:Fluorescence; D017324:Hematoporphyrin Derivative / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D009682:Magnetic Resonance Spectroscopy; D010569:Perylene / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D011166:Porphyrins / Q000737:chemistry / Q000494:pharmacology*; D012710:Serum Albumin, Bovine; D014709:Vero Cells
chemical_list: D000873:Anthracenes; D017319:Photosensitizing Agents; D011166:Porphyrins; C006969:chlorin; D012710:Serum Albumin, Bovine; D010569:Perylene; D017324:Hematoporphyrin Derivative; C004965:hypericin
keywords: Cancer cells; Chlorin derivative; Hematoporphyrin derivative; Hypericin; Photodynamic therapy