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从植物中筛选有希望的化疗候选药物治疗人类成人 T 细胞白血病/淋巴瘤(III)。

Screening of promising chemotherapeutic candidates from plants against human adult T-cell leukemia/lymphoma (III).

机构信息

Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.

出版信息

J Nat Med. 2013 Oct;67(4):894-903. doi: 10.1007/s11418-013-0747-2. Epub 2013 Feb 10.

Abstract

Adult T-cell leukemia/lymphoma (ATL) is a malignancy of mature peripheral T lymphocytes caused by human T-cell lymphotropic virus type I (HTLV-I). In our previous paper, 214 extracts from 162 plants were screened to elucidate the anti-proliferative principles against HTLV-I-infected T-cell lines. In this study, 245 extracts from 182 plants belonging to 61 families were further tested against two HTLV-I-infected T-cell lines (MT-1 and MT-2). Potent anti-proliferative effects were exhibited against MT-1 and MT-2 cells by 52 and 60 of the 245 extracts tested, respectively. Of these, two extracts showed strong inhibitory activity (EC₅₀ values 0.1-1 μg/mL; +++) against both cells, 7 extracts showed moderate inhibitory activity (EC5₅₀ values 1-10 μg/mL; ++), and 43 extracts showed weak inhibitory activity (EC₅₀ values 10-100 μg/mL; +), whereas the remaining extracts did not show any activity (EC₅₀ values >100 μg/mL; -) against MT-1 cells. On the other hand, 10 extracts showed moderate inhibitory activit and, 48 extracts showed weak inhibitory activity, whereas the remaining extracts did not show any activity against MT-2 cells. Extracts from the aerial parts of Annona reticulata and A. squamosa showed the most potent inhibitory activity and three aporphine alkaloids were isolated from their extracts as the active principles by activity-guided fractionation.

摘要

成人 T 细胞白血病/淋巴瘤(ATL)是一种由人类 T 细胞白血病病毒 I 型(HTLV-I)引起的成熟外周 T 淋巴细胞恶性肿瘤。在我们之前的论文中,我们筛选了 162 种植物的 214 种提取物,以阐明针对 HTLV-I 感染的 T 细胞系的抗增殖原理。在这项研究中,我们进一步测试了来自 61 个科的 182 种植物的 245 种提取物对两种 HTLV-I 感染的 T 细胞系(MT-1 和 MT-2)的作用。结果显示,在 245 种提取物中,有 52 种和 60 种分别对 MT-1 和 MT-2 细胞表现出强烈的增殖抑制作用。其中,有两种提取物对两种细胞均表现出强烈的抑制活性(EC₅₀ 值为 0.1-1 μg/mL;+++),7 种提取物表现出中度抑制活性(EC₅₅₀ 值为 1-10 μg/mL;++),43 种提取物表现出弱抑制活性(EC₅₅₀ 值为 10-100 μg/mL;+),而其余提取物对 MT-1 细胞均无活性(EC₅₅₀ 值>100 μg/mL;-)。另一方面,有 10 种提取物对 MT-2 细胞表现出中度抑制活性,48 种提取物表现出弱抑制活性,而其余提取物对 MT-2 细胞均无活性。来自 Annona reticulata 和 A. squamosa 的地上部分的提取物表现出最强的抑制活性,通过活性导向分离,从它们的提取物中分离出三种阿朴啡生物碱作为活性成分。

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