Ras inhibition enhances autophagy, which partially protects cells from death

// Eran Schmukler 1 , Efrat Grinboim 1 , Sari Schokoroy 1 , Adva Amir 1 , Eya Wolfson 1 , Yoel Kloog 1 and Ronit Pinkas-Kramarski 1 1 Department of Neurobiology, Tel-Aviv University, Ramat-Aviv, Israel Correspondence: Ronit Pinkas-Kramarski, email: // Keywords : autophagy, Ras, transformation, signal transduction. Received : October 09, 2012, Accepted : January 17, 2013, Published : January 19, 2013 Abstract Autophagy, a process of regulated turnover of cellular constituents, is essential for normal growth control but may be defective under pathological conditions. The Ras/PI3K/mTOR signaling pathway negatively regulates autophagy. Ras signaling has been documented in a large number of human cancers. In this in-vitro study we examined the effect of the Ras inhibitor Salirasib (S- trans , trans -farnesylthiosalicylic acid; FTS) on autophagy induction and cell viability. We show that Ras inhibition by FTS induced autophagy in several cell lines, including mouse embryonic fibroblasts and the human cancer cell lines HeLa, HCT-116 and DLD-1. The autophagy induced by FTS seems to inhibit the cell death induced by FTS, since in the absence of autophagy the death of FTS-treated cells was enhanced. Therefore, inhibition of autophagy may promote the inhibition of tumor cell growth and the cell death mediated by FTS.