Oxidative Stress-Driven Autophagy acROSs Onset and Therapeutic Outcome in Hepatocellular Carcinoma

Table 2

Molecules tested in HCC cell lines and impinging on ROS/autophagy crosstalk.

Drug	Effect	Role of ROS	Source of oxidative stress	Ref.
Sorafenib	Apoptosis and prosurvival autophagy	Dose-dependent cytostatic and cytotoxic effects; apoptotic cell death	Mitochondrial ROS and GSH depletion	[70, 71]
Oxaliplatin	Apoptosis and prosurvival autophagy	Enhanced apoptotic cell death upon autophagy inhibition	Inhibition of thioredoxin reductase	[76, 92]
Salinomycin	Apoptosis and inhibition of autophagy	Contribution to apoptosis activation	Accumulation of dysfunctional mitochondria due to impaired autophagic flux	[79]
Capsaicin	Apoptosis and induction of cytoprotective STAT3-dependent autophagy	Phosphorylation of STAT3 and activation of autophagy	Inhibition of mitochondrial complexes I and III; reduction of antioxidants (results obtained in pancreatic cancer cells)	[80, 93]
Licochalcone A	Induction of apoptosis and prosurvival ULK1/ATG13-mediated autophagy	Activation of autophagic flux	Suppression of the GSH generation and formation of superoxide	[78]
Bevacizumab	Antiangiogenic effect and induction of prosurvival autophagy	Enhancement of metabolic stress-induced oxidative damage and cytotoxicity	Indirectly obtained by metabolic stress such as starvation and hypoxia	[77]
OSU-03012	Autophagic cell death (ACD)	Activation of autophagic flux	Unknown. Mitochondrial superoxide production was demonstrated for the analogue Celecoxib	[83, 94]
DHEA	ACD	No involvement in autophagic commitment	Decrease of GSH/GSSG ratio and impaired pentose phosphate pathway	[86]
Tetrandrine	Apoptosis (high concentrations) and ACD (low concentrations)	Activation of ERK-mediated autophagic flux	Mitochondrial dysfunction	[87]
Adpa-Mn	Apoptosis and ACD	Induction of both apoptosis and autophagy	Mitochondrial dysfunction	[88]