Photosensitization by hypericin: Electron spin resonance (ESR) evidence for the formation of singlet oxygen and superoxide anion radicals in an in vitro model

Hadjur, Christophe; Jeunet, A.; Jardon, Pierre

doi:10.1016/1011-1344(94)85037-2

Cited by 93 publications

(73 citation statements)

References 22 publications

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“…HY generates a high quantum yield of singlet oxygen (Thomas et al, 1992), superoxide anions (Hadjur et al, 1994) and semiquinone radicals (Weiner and Mazur, 1992;Diwu and Lown, 1993). It was shown to be cytotoxic to fibroblasts (Hadjur et al, 1995) and mammary carcinoma cells in vitro (Thomas and Pardini, 1992).…”

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confidence: 99%

A photodynamic pathway to apoptosis and necrosis induced by dimethyl tetrahydroxyhelianthrone and hypericin in leukaemic cells: possible relevance to photodynamic therapy

et al. 1999

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SummaryThe mechanism of cell death induction by dimethyl tetrahydroxyhelianthrone (DTHe), a new second-generation photodynamic sensitizer, is analysed in human leukaemic cell lines in comparison with the structurally related hypericin. DTHe has a broad range of light spectrum absorption that enables effective utilization of polychromatic light. Photosensitization of HL-60 cells with low doses of DTHe (0.65 µM DTHe and 7.2 J cm -2 light energy) induced rapid apoptosis of ≥90% of the cells. At doses ≥2 µM, dying cells assumed morphological necrosis with perinucleolar condensation of chromatin in HL-60 and K-562 cell lines. Although nuclear fragmentation that is characteristic to apoptosis was prevented, DNA digestion to oligonucleosomes proceeded unhindered. Such incomplete apoptosis was more prevalent with the related analogue hypericin throughout most doses of photosensitization. Despite hypericin being a stronger photosensitizer, DTHe exhibited advantageous phototoxic properties to tumour cells, initiating apoptosis at concentrations about threefold lower than hypericin. Photosensitization of the cells induced dissociation of the nuclear envelope, releasing lamins into the cytosol. DTHe also differed from hypericin in effects exerted on the nuclear lamina, causing release of an 86-kDa lamin protein into the cytosol that was unique to DTHe. Within the nucleus, nuclear envelope lamin B underwent covalent polymerization, which did not affect apoptotic nuclear fragmentation at low doses of DTHe. At higher doses, polymerization may have been extensive enough to prevent nuclear collapse. Hut-78, CD4 + cells were resistant to the photodynamically activated apoptotic pathway. Beyond the tolerated levels of photodynamic damage, these cells died exclusively via necrosis. Hut-78 cells overexpress Bcl-X L as well as a truncated Bcl-X L tr isoform that could contribute to the observed resistance to apoptosis.Keywords: photodynamic therapy; hypericin; dimethyl tetrahydroxyhelianthrone; Bcl-X; Bax; lamin; apoptosis 423British Journal of Cancer (1999) 79(3/4), 423-432 © 1999 Cancer Research Campaign Article no. bjoc.1998 Received Efforts to identify novel efficacious agents for photodynamic therapy led us to evaluate the photodynamically induced cytotoxicities of a newly designed photosensitizer 10,13-dimethyl 1,3,4,6-tetrahydroxyhelianthrone (DTHe) (Figure 1), in leukaemic cell lines. DTHe was chosen because of its dibenzperylenequinone chromophore (seven aromatic rings) that has absorption spectral properties virtually identical to hypocrellins, potent anti-tumoral photosensitizers isolated from the parasitic fungus Hypocrella bambuase which grows in China and Tibet (Diwu, 1990;Diwu, 1995; Miller, 1997). DTHe also shares structural similarities with HY and was anticipated to be a potent photosensitizer owing to its considerable light absorbance in the visible range of the spectrum. The phototoxicity profiles and mechanisms of cell death induction of DTHe were analysed in comparison with those of HY in HL-60, K-562 and Hut-...

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confidence: 99%

A photodynamic pathway to apoptosis and necrosis induced by dimethyl tetrahydroxyhelianthrone and hypericin in leukaemic cells: possible relevance to photodynamic therapy

et al. 1999

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“…Sensitizer triplets, then either react first with substrate and solvent molecules to form reactive free radicals and radical ions, which are oxygenated subsequently (Type I mechanism), or they exchange first excitation with ground state triplet oxygen to generate reactive oxygen species (Type II mechanism). These products include singlet oxygen (102; lag; Jardon et al 1987;Hadjur et al 1994) and superoxide radical anions (0 2; Malkin and Mazur 1993;Hadjur et al 1994). Hypericin-sensitized photodynamic effects have been demonstrated in diverse biological systems.…”

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confidence: 99%

Photodynamic effects of hypericin on photosynthetic electron transport and fluorescence of Anacystis nidulans (Synechococcus 6301)

et al. 1996

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We investigated the photodynamic action of hypericin, a natural naphthodianthrone, on photosynthetic electron transport and fluorescence of the cyanobacterium Anacystis nidulans (Synechococcus 6301). The most drastic effect was the inactivation of photosynthetic oxygen evolution in the presence of the electron acceptor phenyl-p-benzoquinone in aerobic cells which required 1 hypericin/5 chlorophyll a for half-maximal effect. Anaerobic A. nidulans was only partially inactivated and variable chlorophyll a fluorescence remained unperturbed suggesting that photoreaction center II was not a target. Further, hypericin, stimulated photoinduced oxygen uptake in the presence of methylviologen in aerobic cells. This action was less specific than the inactivation of oxygen evolution (1 hypericin/0.5-0.7 chlorophyll a for half-maximal effect). Results point to the involvement of molecular oxygen in two ways. Type I mechanism (Henderson BW and Dougherty TJ (1992) Photochem Photobiol 55: 145-157) in which ground state oxygen reacts with excited substrate triplets appears probable for the inactivation of oxygen evolution. On the other hand, Type II mechanism in which excited oxygen singlets react with ground state substrate molecules appears probable in the stimulation of methylviologen mediated oxygen uptake.

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“…Upon irradiation of air-saturated CH 3 CN solution of complex 1 (1 mM) and TEMP (50 mM) with 355 nm laser, a three-line EPR spectrum with equal intensity and hyperfine coupling constants of a N = 16.0 G was observed, which may be assigned to TEMPO (TEMP-1 O 2 adduct) signal (Fig. 11) [52,53]. Control experiments ensure that O 2 , light, TEMP, and complex are all necessary for the EPR signal.…”

Section: O 2 Generation Ability Comparisonmentioning

confidence: 97%

DNA photocleavage activity of cobalt(III) polypyridyl complexes containing dpq ligand

Sun

Zhou

Chen

et al. 2009

Journal of Inorganic Biochemistry

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Photosensitization by hypericin: Electron spin resonance (ESR) evidence for the formation of singlet oxygen and superoxide anion radicals in an in vitro model

Cited by 93 publications

References 22 publications

A photodynamic pathway to apoptosis and necrosis induced by dimethyl tetrahydroxyhelianthrone and hypericin in leukaemic cells: possible relevance to photodynamic therapy

A photodynamic pathway to apoptosis and necrosis induced by dimethyl tetrahydroxyhelianthrone and hypericin in leukaemic cells: possible relevance to photodynamic therapy

Photodynamic effects of hypericin on photosynthetic electron transport and fluorescence of Anacystis nidulans (Synechococcus 6301)

DNA photocleavage activity of cobalt(III) polypyridyl complexes containing dpq ligand

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