Ras inhibition enhances autophagy, which partially protects cells from death
Metrics: PDF 1910 views | HTML 2276 views | ?
Eran Schmukler1, Efrat Grinboim1, Sari Schokoroy1, Adva Amir1, Eya Wolfson1, Yoel Kloog1 and Ronit Pinkas-Kramarski1
1 Department of Neurobiology, Tel-Aviv University, Ramat-Aviv, Israel
Ronit Pinkas-Kramarski, email:
Keywords: autophagy, Ras, transformation, signal transduction.
Received: October 09, 2012, Accepted: January 17, 2013, Published: January 19, 2013
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.