橄榄苦苷是阿霉素介导的前列腺癌细胞杀伤的强致敏剂,并通过诱导自噬发挥其作用

A. Papachristodoulou, M. Tsoukala, D. Benaki, S. Kostidis, K. Gioti, N. Aligiannis, H. Pratsinis, D. Kletsas, A. Skaltsounis, E. Mikros, R. Tenta
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引用次数: 8

摘要

橄榄苦苷(OLEU)是一种具有生物活性的天然产物,最近显示出抗增殖特性。阿霉素(DXR)是一种蒽环类药物,存在于许多化疗方案中,尽管由于其心脏毒性作用而受到限制。因此,在不影响其抗肿瘤功效的情况下降低DXR毒性的重要研究工作已经投入。采用流式细胞术观察DXR和OLEU对PC-3前列腺癌细胞的抑癌作用,并观察细胞周期分布和凋亡率。通过免疫印迹和免疫荧光染色测定自噬过程。最后,利用核磁共振光谱对细胞提取物进行分析。本研究表明,DXR和OLEU均能抑制PC-3细胞的增殖,而DXR和OLEU共处理则具有加性抑制作用。虽然将OLEU添加到DXR中并没有显著改变细胞周期分布,并且对细胞凋亡率产生了轻微的增加,但两种化合物都产生了显著的自噬诱导作用。此外,处理过的细胞表现出显著的代谢物改变。本研究表明,OLEU作为日常饮食的基本成分,能够显著降低DXR的细胞毒剂量,同时对前列腺癌细胞具有重要的抗增殖作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Oleuropein is a Powerful Sensitizer of Doxorubicin-mediated Killing of Prostate Cancer Cells and Exerts Its Action via Induction of Autophagy
The phenolic component Oleuropein (OLEU), a bioactive natural product, has recently shown antiproliferative properties. Doxorubicin (DXR) is an anthracycline present in many chemotherapeutic schemes, although limited due to its cardio-toxic effects. Important research effort has been devoted therefore, to reducing DXR toxicity without compromising its antitumor efficacy. The anticancer actions of DXR and OLEU were assessed, on PC-3 prostate cancer cells, while cell cycle distribution and rate of apoptosis were assessed by flow cytometry. The autophagic process was determined via immunoblotting and immunofluorescent staining. Finally, cell extracts were analyzed by NMR spectroscopy. The present study showed that both DXR and OLEU inhibited PC-3 cells proliferation, while the co-treatment with DXR and OLEU resulted in an additive inhibition. Although the addition of OLEU to DXR did not alter significantly the cell cycle distribution, exhibited by each treatment alone, and produced a marginal increase on the rate of apoptosis, both compounds produced a remarkable induction of autophagy. In addition, treated cells exhibited significant metabolite alterations. This study demonstrates that OLEU, a basic component of the everyday diet, is capable of lowering significantly the cytotoxic dose of DXR, while obtaining an important anti-proliferative effect in prostate cancer cells.
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