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两种大戟属植物在人类急性髓系白血病中的抗氧化及选择性抗癌活性

Antioxidant and selective anticancer activities of two Euphorbia species in human acute myeloid leukemia.

作者信息

Ben Jannet Soumaya, Hymery Nolwenn, Bourgou Soumaya, Jdey Ahmed, Lachaal Mokhtar, Magné Christian, Ksouri Riadh

机构信息

Laboratoire des Plantes Aromatiques et Médicinales, Centre de Biotechnologie de Borj-Cédria (CBBC), BP 901, 2050 Hammam-Lif, Tunisie; Université de Tunis El Manar, Unité de Physiologie et Biochimie de la Réponse des Plantes aux Contraintes Abiotiques, Département de Biologie, 1068 Tunis, Tunisie.

Laboratoire de Biodiversité et d'Écologie Microbienne (EA 3882), Université de Brest, Parvis Blaise Pascal, 29280 Plouzané, France.

出版信息

Biomed Pharmacother. 2017 Jun;90:375-385. doi: 10.1016/j.biopha.2017.03.072. Epub 2017 Apr 2.

Abstract

In this study, two Euphorbia species (i.e. terracina and paralias) were investigated for their cytotoxic and antioxidant activities. Cytotoxicity of plant methanol and chloroform fractions was examined towards human acute myeloid leukemia (THP1) and human colon epithelial (Caco2) cancer cell lines, as well as CD 14 and IEC-6 normal cells by targeting various modulators of apoptosis or inflammation. Moreover, secondary metabolite pools (phenolic classes, alkaloids, terpenes, saponins) and antioxidant activities (DPPH, ABTS and O- scavenging, as well as FRAP tests) were assessed in plant extracts. Both Euphorbia species appeared to be rich in phenolic compounds and terpenoids, Moreover, E. terracina polar and apolar fractions and E. paralias polar fraction were highly active against THP1 cells, with IC values of 2.08, 14.43 and 54.58μg/mL, respectively. However, no cytotoxicity was found against normal cells (CD14 monocytes). The results indicate that the three fractions induce apoptosis in THP1 cell line after 6h of exposure. Furthermore, apoptosis caused by apolar fraction was related to a caspase-dependent process, whereas other death pathways seemed to be involved with the polar fractions. An enhanced production of reactive oxygen species was detected upon cell treatment with plant extracts. Interestingly, they have no effect on cytokine TNF-α secretion in THP1 and normal cells compared to untreated cells, indicating that the three fractions caused no inflammation. Euphorbia terracina and E. paralias polar fractions showed strong antioxidant activity with potent scavenging capacity against DPPH, ABTS and superoxide radicals. Moreover, these fractions displayed a very high ferric reducing power. These findings confirm the strong antioxidant capacity of Euphorbia plants and suggest a targeted anti-cancer effect with a potent anti-proliferative property of E. terracina and E. paralias extracts, which induce programmed cell death in leukemia cell lines but not in normal monocytes cells.

摘要

在本研究中,对两种大戟属植物(即滨海大戟和海滨大戟)的细胞毒性和抗氧化活性进行了研究。通过靶向凋亡或炎症的各种调节因子,检测了植物甲醇和氯仿组分对人急性髓系白血病(THP1)和人结肠上皮(Caco2)癌细胞系以及CD 14和IEC - 6正常细胞的细胞毒性。此外,还评估了植物提取物中的次生代谢产物库(酚类、生物碱、萜类、皂苷)和抗氧化活性(DPPH、ABTS和超氧阴离子清除以及FRAP试验)。两种大戟属植物似乎都富含酚类化合物和萜类化合物。此外,滨海大戟的极性和非极性组分以及海滨大戟的极性组分对THP1细胞具有高活性,IC值分别为2.08、14.43和54.58μg/mL。然而,未发现对正常细胞(CD14单核细胞)有细胞毒性。结果表明,这三个组分在暴露6小时后可诱导THP1细胞系凋亡。此外,非极性组分引起的凋亡与半胱天冬酶依赖性过程有关,而其他死亡途径似乎与极性组分有关。在用植物提取物处理细胞后,检测到活性氧的产生增加。有趣的是,与未处理的细胞相比,它们对THP1和正常细胞中的细胞因子TNF-α分泌没有影响,表明这三个组分不会引起炎症。滨海大戟和海滨大戟的极性组分表现出很强的抗氧化活性,对DPPH、ABTS和超氧阴离子自由基具有强大的清除能力。此外,这些组分表现出非常高的铁还原能力。这些发现证实了大戟属植物具有很强的抗氧化能力,并表明滨海大戟和海滨大戟提取物具有靶向抗癌作用,具有强大的抗增殖特性,可诱导白血病细胞系程序性细胞死亡,但对正常单核细胞无此作用。

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