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.
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DOI：
10.1038/sj.bjc.6690066
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发表时间：
1999-02
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
通过与结构相关的金丝桃素进行比较，分析了新型第二代光动力敏化剂二甲基四羟基千日酮 (DTHe) 在人类白血病细胞系中诱导细胞死亡的机制。 DTHe 具有广泛的光谱吸收能力，可以有效利用多色光。低剂量 DTHe（0.65 μM DTHe 和 7.2 J cm−2 光能）对 HL-60 细胞进行光敏化，诱导 ≥90% 的细胞快速凋亡。在剂量≥2 μM时，HL-60和K-562细胞系中垂死细胞呈现形态学坏死，并伴有核仁周围染色质浓缩。尽管细胞凋亡特有的核断裂被阻止，但 DNA 消化成寡核小体的过程却不受阻碍。在大多数剂量的光敏作用中，相关类似物金丝桃素更容易发生这种不完全细胞凋亡。尽管金丝桃素是一种更强的光敏剂，DTHe 对肿瘤细胞表现出有利的光毒性特性，在比金丝桃素低约三倍的浓度下引发细胞凋亡。细胞的光敏作用诱导核膜解离，将核纤层蛋白释放到细胞质中。 DTHe 与金丝桃素的不同之处还在于它对核纤层的影响，导致 86 kDa 的核纤层蛋白释放到细胞质中，这是 DTHe 所特有的。在细胞核内，核膜核纤层蛋白 B 发生共价聚合，这在低剂量 DTHe 下不影响细胞凋亡的核碎裂。在较高剂量下，聚合可能已经足够广泛以防止核崩溃。 Hut-78、CD4+细胞对光动力激活的凋亡途径具有抵抗力。超出光动力损伤的耐受水平，这些细胞仅通过坏死而死亡。 Hut-78 细胞过度表达 Bcl-XL 以及截短的 Bcl-XL tr 同种型，这可能有助于观察到的细胞凋亡抵抗力。 © 癌症研究运动
The 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-XL as well as a truncated Bcl-XL tr isoform that could contribute to the observed resistance to apoptosis. © Cancer Research Campaign
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影响因子：
1.5
作者：
DEGAR, S;PRINCE, AM;MERUELO, D
通讯作者：
MERUELO, D
影响因子：
5.8
作者：
AGOSTINIS, P;VANDENBOGAERDE, A;DEWITTE, P
通讯作者：
DEWITTE, P
影响因子：
7.6
作者：
HUDSON, JB;HARRIS, L;TOWERS, GHN
通讯作者：
TOWERS, GHN
DOI：
10.1016/0047-2670(84)80001-5
发表时间：
1984-01-01
期刊：
JOURNAL OF PHOTOCHEMISTRY
影响因子：
--
作者：
CHATTOPADHYAY, SK;KUMAR, CV;DAS, PK
通讯作者：
DAS, PK
DOI：
10.1016/1011-1344(94)07064-u
发表时间：
1995-02-01
影响因子：
5.4
作者：
HADJUR, C;RICHARD, MJ;JARDON, P
通讯作者：
JARDON, P