Propranolol sensitizes prostate cancer cells to glucose metabolism inhibition and prevents cancer progression.
Propranolol sensitizes prostate cancer cells to glucose metabolism inhibition and prevents cancer progression.
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DOI：
10.1038/s41598-018-25340-9
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发表时间：
2018-05-04
影响因子：
4.6
通讯作者：
Deroanne CF
中科院分区：
文献类型：
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作者：
Brohée L;Peulen O;Nusgens B;Castronovo V;Thiry M;Colige AC;Deroanne CF
心得安是一种广泛使用的非选择性β-肾上腺素能受体阻滞剂，最近被证明具有抗癌作用。还概述了它与某些药物协同作用的潜力。然而，有必要考虑心得安的所有性质，以选择能够有效结合的药物。据报道，心得安可以阻断自噬的晚期。因此，我们假设在增强自噬通量的条件下，癌细胞应该对心得安特别敏感。2DG是一种糖酵解抑制剂，是一种抗肿瘤药物，在单一治疗中效果有限，主要是由于诱导了有利于生存的自噬。在这里，我们报告了心得安与糖酵解抑制剂2DG联合治疗癌细胞时，由于自噬阻断，导致自噬小体大量积累。普萘洛尔+2DG在体外能有效地抑制前列腺癌细胞增殖，诱导细胞凋亡，改变线粒体形态，抑制线粒体生物能量学，加重内质网应激，抑制体内肿瘤生长。我们的研究首次强调了利用心得安抑制自噬的能力来设计新的抗癌疗法的兴趣。
Propranolol, a widely used non-selective beta-adrenergic receptor blocker, was recently shown to display anticancer properties. Its potential to synergize with certain drugs has been also outlined. However, it is necessary to take into account all the properties of propranolol to select a drug that could be efficiently combined with. Propranolol was reported to block the late phase of autophagy. Hence, we hypothesized that in condition enhancing autophagy flux, cancer cells should be especially sensitive to propranolol. 2DG, a glycolysis inhibitor, is an anti-tumor agent having limited effect in monotherapy notably due to induction of pro-survival autophagy. Here, we report that treatment of cancer cells with propranolol in combination with the glycolysis inhibitor 2DG induced a massive accumulation of autophagosome due to autophagy blockade. The propranolol +2DG treatment efficiently prevents prostate cancer cell proliferation, induces cell apoptosis, alters mitochondrial morphology, inhibits mitochondrial bioenergetics and aggravates ER stress in vitro and also suppresses tumor growth in vivo. Our study underlines for the first time the interest to take advantage of the ability of propranolol to inhibit autophagy to design new anti-cancer therapies.
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影响因子：
29
作者：
Kimmelman AC;White E
通讯作者：
White E
影响因子：
2.9
作者：
LABARCA, C;PAIGEN, K
通讯作者：
PAIGEN, K
影响因子：
11.2
作者：
Furuta, Eiji;Okuda, Hiroshi;Kobayashi, Aya;Watabe, Kounosuke
通讯作者：
Watabe, Kounosuke
影响因子：
3.7
作者：
Deroanne, CF;Colige, AC;Lapiere, CM
通讯作者：
Lapiere, CM
DOI：
10.1038/nrurol.2014.196
发表时间：
2014-09
期刊：
Nature reviews. Urology
影响因子：
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作者：
通讯作者：
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