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叶绿素相关化合物脱镁叶绿酸a对ICR小鼠皮肤肿瘤促进作用的抑制效果

Inhibitory effect of pheophorbide a, a chlorophyll-related compound, on skin tumor promotion in ICR mouse.

作者信息

Nakamura Y, Murakami A, Koshimizu K, Ohigashi H

机构信息

Department of Food Science and Technology, Faculty of Agriculture, Kyoto University, Japan.

出版信息

Cancer Lett. 1996 Nov 29;108(2):247-55. doi: 10.1016/s0304-3835(96)04422-9.

DOI:10.1016/s0304-3835(96)04422-9
PMID:8973602
Abstract

Anti-tumor-promoting activity of pheophorbide a (PPBa) a chlorophyll-related compound, was examined in a two-stage carcinogenesis experiment in ICR mouse skin by 7,12-dimethylbenz[a] anthracene (DMBA, 0.19 mumol) and 12-O-tetradecanoylphorbol-13-acetate (TPA, 1.6 nmol). Topical application of PPBa (160 nmol) markedly reduced the average number of tumors per mouse and the ratio of tumor-bearing mice (inhibitory ratio: IR = 56%, P < 0.01 and 31%, P < 0.005, respectively). PPBa exhibited potent anti-inflammatory activity in ICR mouse ears and moderate inhibitory activity toward TPA-induced superoxide (O2-) generation in differentiated HL-60 cells. While CuPPBa, a synthetic copper complex of PPBa, exhibited higher anti-inflammatory activity than that of indomethacin, it showed little antioxidative effect against formation of lipid hydroperoxides (LOOHs) and malondialdehyde (MDA), suggesting that the antioxidative effect of PPBa might not be important for anti-inflammatory activity. These results imply that the active mechanism of PPBa for anti-tumor promotion might be partly involved in inhibition of TPA-induced inflammatory responses by suppressing leukocyte activation.

摘要

脱镁叶绿酸a(PPBa)是一种与叶绿素相关的化合物,在ICR小鼠皮肤的两阶段致癌实验中,研究了其抗肿瘤促进活性。该实验采用7,12-二甲基苯并[a]蒽(DMBA,0.19 μmol)和12-O-十四烷酰佛波醇-13-乙酸酯(TPA,1.6 nmol)。局部应用PPBa(160 nmol)显著降低了每只小鼠的平均肿瘤数量和荷瘤小鼠的比例(抑制率:IR分别为56%,P < 0.01和31%,P < 0.005)。PPBa在ICR小鼠耳部表现出强大的抗炎活性,对分化的HL-60细胞中TPA诱导的超氧阴离子(O2-)生成具有中等抑制活性。虽然PPBa的合成铜配合物CuPPBa表现出比吲哚美辛更高的抗炎活性,但它对脂质氢过氧化物(LOOHs)和丙二醛(MDA)的形成几乎没有抗氧化作用,这表明PPBa的抗氧化作用可能对抗炎活性并不重要。这些结果表明,PPBa抗肿瘤促进的活性机制可能部分涉及通过抑制白细胞活化来抑制TPA诱导的炎症反应。

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