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Preclinical Antileukemia Activity of Tramesan: A Newly Identified Bioactive Fungal Metabolite

机译:曲美素的临床前抗白血病活性:一种新鉴定的生物活性真菌代谢物

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摘要

Despite improvements that occurred in the last decades in the acute myeloid leukemia (AML) treatment, clinical results are still unsatisfactory. More effective therapies are required, and innovative approaches are ongoing, including the discovery of novel antileukemia natural compounds. Several studies have described the activity of extracts from mushrooms which produce compounds that exhibited immunological and antitumor activities. The latter has been demonstrated to be promoted in vitro by mushroom polysaccharides via induction of apoptosis. However, the antileukemia activity of these compounds on primary cells is still not reported. In the present study, we examined the in vitro effects of Tramesan (TR), a bioactive compound extracted from Trametes versicolor, on leukemic cell lines and primary cells. Our results demonstrated that TR induced a marked growth inhibition of leukemic cell lines and primary cells from AML patients. The antiproliferative effects of TR were associated in primary AML cells with a significant increase of apoptosis. No significant cytotoxic effects were observed in normal peripheral blood mononuclear cells (MNC) from healthy donors. Our data demonstrated a cytotoxic activity of TR on leukemia cells prompting further translational applications. Ongoing studies are elucidating the molecular mechanisms underlying its antileukemic activity.
机译:尽管在过去的几十年中,急性髓细胞白血病(AML)的治疗有所改善,但临床结果仍不能令人满意。需要更有效的疗法,并且创新的方法正在开发中,包括发现新型抗白血病天然化合物。数项研究描述了蘑菇中提取物的活性,这些蘑菇产生的化合物具有免疫和抗肿瘤活性。已证明后者可通过诱导细胞凋亡由蘑菇多糖体外促进。然而,这些化合物对原代细胞的抗白血病活性仍未报道。在本研究中,我们检查了曲美素(TR)(一种从云芝Trametes提取的生物活性化合物)对白血病细胞系和原代细胞的体外作用。我们的结果证明TR可以显着抑制AML患者的白血病细胞系和原代细胞的生长。 TR的抗增殖作用在原代AML细胞中与凋亡的显着增加有关。在健康捐献者的正常外周血单核细胞(MNC)中未观察到明显的细胞毒性作用。我们的数据表明TR对白血病细胞具有细胞毒活性,促使进一步的翻译应用。正在进行的研究正在阐明其抗白血病活性的分子机制。

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