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

Kapoor, Vaishali; Zaharieva, Maya M.; Das, Satya N.; Berger, Martin R.

doi:10.1016/j.canlet.2011.12.032

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Volume 319, Issue 1 , Pages 39-48, 1 June 2012

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

Vaishali Kapoor
- Toxicology and Chemotherapy Unit, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany
- Tumor Biology and Molecular Immunology Laboratory, Department of Biotechnology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India
Maya M. Zaharieva
- Toxicology and Chemotherapy Unit, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany
Satya N. Das
- Tumor Biology and Molecular Immunology Laboratory, Department of Biotechnology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India
Martin R. Berger
- Toxicology and Chemotherapy Unit, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany
- Corresponding author.

Received 28 September 2011; received in revised form 16 December 2011; accepted 16 December 2011. published online 09 January 2012.

Abstract

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.

Keywords: Oral squamous cell cancer, mTOR signaling cascade, Alkylphosphocholine, Erufosine, Autophagy