Autophagy induction as an efficient strategy to eradicate tumors

Autophagy
Vega García-Escudero, Ricardo Gargini

Abstract

The understanding of the mechanisms of cell-death execution and the role that they play in different diseases opens new therapeutic strategies. Currently, increasing evidence indicates that autophagy is a frequent cell-death mechanism, so the question arises: Could autophagy stimulation be considered an antitumor therapy? Several autophagy inducers have been used as anticancer agents and, although complete tumor eradication has not been demonstrated, the antitumor effect is very promising. We have recently demonstrated that strong autophagy stimulation mediated by the combined generation of cyanide and oxidative stress could efficiently suppress tumor growth in an aggressive brain cancer model such as glioblastoma. We have used the plant enzyme linamarase, which metabolizes the innocuous substrate linamarin to generate cyanide in a continuous and controlled way inducing mitochondrial fragmentation. Glucose oxidase addition induces oxidative stress that increases cell vacuolization. The combination of both insults favors mitochondrial engulfment by vacuoles accelerating cell death that is mediated by autophagy.

Citations

Aug 16, 2011·Journal of Neuro-oncology·Jean M Mulcahy Levy, Andrew Thorburn
Oct 29, 2011·Clinical Oncology : a Journal of the Royal College of Radiologists·A L SwampillaiS C Short
Mar 29, 2011·Pharmacology & Therapeutics·Jean M Mulcahy Levy, Andrew Thorburn
Oct 5, 2013·Autophagy·Haiqi LuHongchuan Jin
Mar 10, 2016·Oncotarget·Lukas JenneweinMichel Mittelbronn
Apr 2, 2016·Oncology Reports·Ricardo GarginiFrancisco Wandosell
Sep 13, 2012·Experimental and Therapeutic Medicine·Xinna WangChuanshan Xu
Aug 28, 2021·International Journal of Molecular Sciences·Leila JahangiriLoukia Tsaprouni

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