Combination of N-(4-hydroxyphenyl) retinamide and apigenin suppressed starvation-induced autophagy and promoted apoptosis in malignant neuroblastoma cells.
Combination of N-(4-hydroxyphenyl) retinamide and apigenin suppressed starvation-induced autophagy and promoted apoptosis in malignant neuroblastoma cells.
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DOI：
10.1016/j.neulet.2011.07.016
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发表时间：
2011-09-08
影响因子：
2.5
通讯作者：
Ray SK
中科院分区：
文献类型：
--
作者：
Mohan N;Banik NL;Ray SK
自噬是恶性肿瘤中代谢应激反应中细胞内容物再循环的分解代谢过程。研究了合成类维甲酸N-（4-羟基苯基）维甲酸（4-HPR）和异黄酮芹菜素（APG）对血清饥饿的人恶性神经母细胞瘤细胞的作用。0.5 μM 4-HPR和50 μM APG联合使用可协同降低血清缺乏的神经母细胞瘤SH-SY5Y、SK-N-BE2和IMR-32细胞的细胞活力。吖啶橙（AO）染色和LC3 II上调表明，血清饥饿12和24 h后，SH-SY5Y细胞酸性囊泡细胞器（AVO）的形成和自噬逐渐增加。此外，AO染色和流式细胞术显示，0.5 μM 4-HPR和50 μM APG联合作用于血清饥饿的SH-SY5Y细胞后，分别阻断了AVO的形成和自噬群体的积累。联合治疗下调自噬诱导蛋白Beclin 1、LC3 II、TLR-4和Myd88，上调自噬抑制p-Akt/mTOR信号通路。与抑制自噬诱导细胞凋亡的假设一致，我们发现，在血清饥饿的SH-SY5Y细胞中，联合治疗后自噬抑制和凋亡诱导表现为生存因子NF-κB的抑制、促凋亡Bax的上调、抗凋亡Bcl-2的下调、caspase-3的激活和聚adp核糖聚合酶（PARP）的降解。4-HPR与APG联合抑制人恶性神经母细胞瘤细胞自噬，促进细胞凋亡。
Autophagy is a catabolic process for recycling of cellular contents in response to metabolic stress in malignant tumors. We explored efficacy of the synthetic retinoid N-(4-hydroxyphenyl) retinamide (4-HPR) and the isoflavonoid apigenin (APG) in the serum-starved human malignant neuroblastoma cells. Combination of 0.5 μM 4-HPR and 50 μM APG synergistically decreased cell viability in the serum-starved neuroblastoma SH-SY5Y, SK-N-BE2, and IMR-32 cells. Acridine orange (AO) staining and LC3 II upregulation showed that serum-starvation for 12 and 24 h progressively increased formation of acidic vesicular organelles (AVO) and autophagy in SH-SY5Y cells. Further, AO stainning and flow cytometry showed blockage of formation of AVO and accumulation of auophagic population, respectively, following treatment of the serum-starved SH-SY5Y cells with combination of 0.5 μM 4-HPR and 50 μM APG. Combination therapy down regulated autophagy inducing proteins such as Beclin 1, LC3 II, TLR-4, and Myd88 while upregulated autophagy inhibitory p-Akt/mTOR singaling pathway. Consistent with the hypothesis that inhibition of autophagy could induce apoptosis, we noticed inhibition of autophagy and induction of apoptosis in the serum-starved SH-SY5Y cells with suppression of the survival factor NF-κB, upregulation of pro-apoptotic Bax, down regulation of anti-apoptotic Bcl-2, activation of caspase-3, and degradation of poly(ADP-ribose) polymerase (PARP) after combination therapy. Collectively, combination of 4-HPR and APG worked synergistically to suppress autophagy and promote apoptosis in human malignant neuroblastoma cells.
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影响因子：
7.8
作者：
Degtyarev, Michael;De Maziere, Ann;Orr, Christine;Lin, Jie;Lee, Brian B.;Tien, Janet Y.;Prior, Wei W.;van Dijk, Suzanne;Wu, Hong;Gray, Daniel C.;Davis, David P.;Stern, Howard M.;Murray, Lesley J.;Hoeflich, Klaus P.;Klumperman, Judith;Friedman, Lori S.;Lin, Kui
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作者：
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影响因子：
3.3
作者：
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通讯作者：
Ohsumi, Y
影响因子：
5.8
作者：
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通讯作者：
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