Targeting Oncogene-Induced Autophagy: A New Approach in Cancer Therapy?

Table 1

Chemical modulators of autophagy and their modes of action.

Compound	Mechanism	Cancer type	Role of autophagy	References
Inducers of autophagy
AZD8055	Inhibits mTORC1 activity	Nonsmall cell lung cancer	Prodeath	[34]
Bortezomib	Blocks Bax degradation	Chronic lymphocytic leukemia	Prodeath	[35]
Bufalin	Synergizes with JNK pathway and increases expression of TNF, BECN-1, MAPK, and ATG8	Liver cancer; Colorectal cancer	Prodeath; Prodeath	[36]; [37]
Chlorpromazine	Inhibits PI3K/Akt/mTOR signaling pathway	Brain cancer	Prodeath	[38]
Cisplatin	Activation of AMPK signaling pathway	Liver cancer	Prodeath	[39]
Compound C (Dorsomorphin)	Inhibits AMPK activity	Colorectal cancer	Prodeath	[40]
Everolimus	Inhibits mTORC1 activity	Acute lymphoblastic leukemia; Prostate cancer	Prodeath; Prodeath	[41]; [42]
Fangchinoline	Transactivation of sestrin2 gene, leading to AMPK signaling activation	Liver cancer	Prodeath	[43]
Imatinib	Increases expression of Beclin-1 and ATG5	Chronic myeloid leukemia; Gastrointestinal stromal tumor	Prodeath; Prosurvival	[44]; [45]
Nilotinib	Induces PP2A-regulated AMPK phosphorylation and activation	Liver cancer	Prodeath	[46]
Obatoclax (GX15-070)	Induces ATG5-dependent autophagic cell death	Acute lymphoblastic leukemia	Prodeath	[47]
Pemetrexed	Increases levels of Akt, p70 S6K, and/or phosphorylated-mTOR	Nonsmall cell lung cancer	Prodeath	[48]
Perifosine	Inhibits PI3K/Akt/mTOR signaling pathway	Chronic myeloid leukemia	Prosurvival	[49]
PI-103 hydrochloride	Inhibits PI3K/Akt/mTOR signaling pathway	Brain cancer	Prodeath	[50]
PP242	Inhibits mTORC1 activity	Multiple cancers	Prodeath	[51]
Resveratrol	Accumulation of intracellular calcium and activation of AMPK/mTOR signaling pathway	Nonsmall cell lung cancer	Prodeath	[52]
Safingol	Increases ROS and/or AMPK activation; Inhibits PKCs and PI3K pathway directly	Breast cancer; Colorectal cancer	Prodeath; Prodeath	[53]; [54]
Salinomycin	Increases ER stress via ATF4-DDIT3/CHOP-TRIB3-Akt-mTOR signaling pathway	Nonsmall cell lung cancer	Prodeath	[55]
Sodium selenite	Activates Nrf2; Dephosphorylates PP2A and lead to DAPK activation	Nonsmall cell lung cancer; Promyelocytic leukemia	Prosurvival; Prodeath	[56]; [57]
Sorafenib; SC-59 (Sorafenib derivative)	Inhibits phospho-STAT3 signaling pathway and reduces expression of myeloid cell leukemia (MCL-1), which disrupts Beclin-1-Mcl-1 complex	Brain, breast, liver, and lung cancers	Prodeath; Prodeath	[48]; [58]
STF-62247	PI3K signaling pathway and golgi trafficking	VHL-deficient renal cancer	Prodeath	[33]
Temsirolimus	Inhibits mTORC1 activity	Mantle cell lymphoma	Prodeath	[59]
Torin-1	ATP-competitive mTOR inhibitor that inhibits both mTORC1 and mTORC2 directly	Multiple cancers	Prodeath	[60]
Wogonin	Inhibits p70S6K/Akt pathway	Nasopharyngeal cancer	Prodeath	[61]
Inhibitors of autophagy
3-Methyladenine (3-MA)	Inhibits PI3K signaling pathway	Colorectal cancer; Esophageal cancer	Prosurvival; Prosurvival	[62]; [63]
Bafilomycin A1	Prevents fusion of autophagosomes with lysosomes by acting as a V-ATPase inhibitor	Breast cancer; Colorectal cancer	Prosurvival; Prosurvival	[64]; [65]
Chloroquine	Inhibits lysosomal acidification and prevents fusion of autophagosomes with lysosomes	Brain cancer; Colorectal cancer	Prosurvival; Prosurvival	[66]; [67]
Lucanthone	Induces vacuolization and interferes with lysosomal function	Breast cancer	Prodeath	[68]
Spautin-1	Promotes ubiquitylation of Beclin-1	Breast cancer	Prodeath	[69]