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siRNA Electroporation to Modulate Autophagy in Herpes Simplex Virus Type 1-Infected Monocyte-Derived Dendritic Cells
Published on: October 28, 2019
Ras inhibition enhances autophagy, which partially protects cells from death
Eran Schmukler1, Efrat Grinboim, Sari Schokoroy
1Department of Neurobiology, Tel-Aviv University, Ramat-Aviv, Israel.
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.
Insights
Ras inhibition by Salirasib (FTS) induces autophagy, a cellular process. This autophagy appears to protect cancer cells from FTS-induced death, suggesting autophagy inhibition could enhance anti-tumor effects.
Area of Science:
- Cellular biology
- Cancer research
Background:
- Autophagy is crucial for cell growth but can be dysfunctional in diseases.
- The Ras/PI3K/mTOR pathway inhibits autophagy and is implicated in many cancers.
Purpose of the Study:
- To investigate the effect of the Ras inhibitor Salirasib (FTS) on autophagy induction and cancer cell viability.
Main Methods:
- In vitro study using mouse embryonic fibroblasts and human cancer cell lines (HeLa, HCT-116, DLD-1).
- Treatment with Salirasib (FTS) to inhibit Ras signaling.
Main Results:
- Salirasib (FTS) treatment induced autophagy in tested cell lines.
- Autophagy inhibited FTS-mediated cell death; its absence enhanced cell death.
Conclusions:
- Ras inhibition by FTS induces autophagy.
- Inhibiting autophagy may enhance tumor cell growth inhibition and FTS-mediated cell death.
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