I rather tend to describe autophagy as a survival mechanism, not a death mechanism. According to many experiments, it seems that autophagy is activated when apoptosis is somehow blocked/inhibited. So, it seems that it is a kind of reservoir to kill the cells when the natural cell death mechanism (apoptosis) is not operational. Therefore, i am not sure if activating autophagy would be reasonable?. We rather try to block it for more efficient cytotoxic effect.  

I would suggest hydroxychloroquine.

The decreased level of ATP in the cell is responsible for undergoing autophagy, apoptosis and programmed necrosis, respectively, Autophagy can promote or inhibit programmed apoptotic and necrotic cell death. Autophagy can promote both cell survival and cell death which can also undergo as autophagic programmed death.

I agree with Engin Ulukaya that autophagy is a survival-promoting pathway.

I do not agree that autophagy is only a survival-promoting process.  Autophagic cell death is responsible for death occurring in cells on autophagy pathway

Interesting discussion. I have seen both pro-survival and pro-death by activating autophagy in my experiments. We tend to simplify a mechanism into good or bad and forget about in biologic system nothing will be 100%. Worst of all is the fact that scientists induce, or activate, a system for 30 minutes or 2 hours to see the effect then claim the major findings in elite journals but never bother to find out what will happen if we keep activating the system for days. One of the system I studied people use 100-1000 fold concentration to activate the system in vitro and never mentioned the same amount will kill all patients in days. We try to manipulate the homeostasis so that modulate the system in our favor is what we can do.

Autophagy is basally active in cells. In response to stress conditions a number of pro-survival pathways, including autophagy, are activated to help the cell cope with stress. However, if stress persists or if it cannot be resolved, then the cell dies by apoptosis (through the priming of the mitochondrial pathway and caspase-9 activation). As such during stress-induced cell death you can detect both features of autophagy and apoptosis. It is well established that when caspases are activated they cleave some of the autophagy proteins and block the process. As such when caspases are activated the autophagy stops. We decided to uncouple the two processes. We primarily deal with ER stress in our studies, a well-known inducer of autophagy and cell death (autophagy is detected by 12 hours post treatment, and cell death at 36h). We recently showed that during ER stress, knockdown of the components of the autophagy machinery (e.g., ATG5 or ATG7) cells are sensitized to apoptosis. As such autophagy is pro-survival.

However, if we compromised apoptotic machinery (e.g., knocking down Bax/Bak or caspase-9) prior to inducing ER stress, we got a more robust induction of autophagy, cells stay around much longer (72 h), but the still died. If we further knockdown ATG5 or ATG7 we blocked cell death. As such in cells in which apoptotic machinery is compromised, autophagy cannot be kept in check and leads to cell death. These cell died by an ATG5, FADD and caspase-8 medicated mechanism. These proteins formed a complex leading to the activation of caspase-8 and cell death (see the link below for our paper published in Autophagy). (http://www.tandfonline.com/action/doSearch?quickLinkJournal=&journalText=&AllField=samali&publication=47006396).

So if you want to induce autophagy-medicated cell death, block the apoptotic pathway (use caspase-inhibitors, knockdown caspase-9 or apaf-1), then you switch autophagy to its lethal mode. This may take much longer. It is best to do colony formation assay.

Good luck with your studies.

I do not know in humans (cancer, neurological patients, in whom induced autophagy could possibly be beneficial) but in animals (young female adult and weanling rats), we were able to induce hepatic autophagy (as demonstrated by EM, cytochemistry) by intense stress for 48 hours or less and the rats were able to recover. Moreover, we were capable of preventing the hepatic autophagy (even though we carried out multiple endocrine, biochemical, physiological and macroscopic examinations of the body, key organs, we do not know if autophagy occurred in brain, other organs)/other (stress) triad modifications induced by intense stress by inhibiting certain other key (stress-induced) physiological parameters. So, in vivo, if the humans (patients) responded similarly, we may be able to possibly induce and control autophagy.