Erufosine simultaneously induces apoptosis and autophagy by modulating the Akt-mTOR signaling pathway in oral squamous cell carcinoma

被引:53
作者
Kapoor, Vaishali [1 ,2 ]
Zaharieva, Maya M. [1 ]
Das, Satya N. [2 ]
Berger, Martin R. [1 ]
机构
[1] German Canc Res Ctr, Toxicol & Chemotherapy Unit, D-69120 Heidelberg, Germany
[2] All India Inst Med Sci, Tumor Biol & Mol Immunol Lab, Dept Biotechnol, New Delhi, India
关键词
Oral squamous cell cancer; mTOR signaling cascade; Alkylphosphocholine; Erufosine; Autophagy; ANTINEOPLASTIC ACTIVITY; TRANSLATION INITIATION; ALKYLPHOSPHOCHOLINE; LINES; ERUCYLPHOSPHOCHOLINE; ERUCYLPHOSPHOHOMOCHOLINE; COMBINATION; EXPRESSION; INHIBITORS; LIPOSOMES;
D O I
10.1016/j.canlet.2011.12.032
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We investigated the anticancer activity of erufosine in oral squamous carcinoma cell lines in terms of cell proliferation, colony formation, induction of autophagy/apoptosis, cell cycle and mTOR signaling pathway. Erufosine showed dose-dependent cytotoxicity in all cell lines, it induced autophagy as well as apoptosis, G2 cell cycle arrest and modulation of cyclin D1 expression. Further erufosine downregulated the phosphorylation of major components of mTOR pathway, like p-Akt at Ser473 and Thr308 residues, p-Raptor, p-mTOR, p-PRAS40 and its downstream substrates p-p70S6K and p-4EBP1 in a dose-dependent manner. The pre-treatment of tumor cells with p-mTOR siRNA increased cytotoxic effects of erufosine comparable to cisplatin but higher than rapamycin. (c) 2011 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:39 / 48
页数:10
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