Table 1.

Role and mechanism of autophagy modulators in various types of skin cancer.

Compound name	Mechanism of action	Skin cancer types	References
Curcumin (diferuloylmethane)	Downregulation of the Akt/mTOR signaling pathway and ROS generation and upregulation of Beclin 1	Melanoma	50
Panduratin A	Downregulation of the mTOR pathway and activation of the AMPK pathway	Melanoma	51
Apigenin	Downregulation of the mTOR pathway and activation of the AMPK pathway	Keratinocyte carcinoma	52
Sinomenine	Inhibition of the PI3K/Akt/mTOR pathway and increased expression of Beclin 1 and LC3-II/LC3-I	Melanoma	53
α-Mangostin	Inhibition of the PI3K/Akt/mTOR pathway and increased expression of Beclin 1, LC3-I, and LC3-II	Melanoma	54
Polyphyllin I	Inhibition of the PI3K/Akt/mTOR pathway and increased expression of Beclin 1, LC3, and LC3-II	Melanoma	55
Physalin A	Upregulation of the p38-NF-κB pathway, increased expression of Beclin 1, and regulation of LC3-II/LC3-I	Melanoma	56
Resveratrol	Modulation of Rictor and suppression of the Akt/mTOR pathway	Squamous cell carcinoma and melanoma	57,58
Erufosine	Inhibition of the Akt/mTOR pathway	Squamous cell carcinoma	59
Harmine	Suppression of the Akt/mTOR pathway	Melanoma	60
Sasanquasaponin III	Inhibition of the Akt/mTOR/p70S6K pathway, ROS accumulation, and upregulation of LC3-II expression	Melanoma	61
Ellagic acid	Inhibition of the PI3K/Akt/mTOR pathway	Melanoma	62
Dihydroartemisinin	Increased accumulation of autophagosomes	Tongue squamous cell carcinoma	63
Thymoquinone	Increased accumulation of autophagosomes	Head and neck squamous cell carcinoma	64
Protoapigenone	ROS generation and increased p53 and Beclin 1 expression	Melanoma	65
Graveoline	ROS generation and increased p53 and Beclin 1 expression	Melanoma	66
Shikonin	ROS generation, activation of the p38 pathway, and increased p-p38, LC3B-II, and Beclin 1 expression	Melanoma	67
Flavokawain B	ROS generation, mTOR inhibition, and increased LC3-II levels	Melanoma	68
Novel ECG analog 4-(S)-(2,4,6-trimethylthiobenzyl)-epigallocatechin gallate	ROS accumulation	Melanoma	69
Usnic acid	ROS generation	Melanoma	70
Icariside II	ROS generation and inhibition of the MITF, JAK-STAT3, and MAPK pathways	Melanoma	71,72
Kalantuboside B	ROS generation, p53 downregulation, and LC3-II accumulation	Melanoma	73
β-β-Dimethylacrylshikonin	ROS generation and increased LC3B-II expression	Melanoma	74
3′-Hydroxydaidzein	Up-regulation of ATG5	Melanoma	75
Luteolin	Activation of acidic lysosomal vacuolization and accumulation of LC3-II	Squamous cell carcinoma	75
Silibinin	Inhibition of the IGF-1R pathway and increased Beclin 1 and ATG5 expression	Epidermoid carcinoma	76
Pterostilbene	Activation of ULK1 and ATG13 by activating the AMPK pathway	Melanoma	77
Silvestrol	Autophagosome formation and accumulation of LC3-II	Melanoma	78
Dorsomorphin	ROS generation and LC3-II expression	Basal cell carcinoma	79
Polygonatum cyrtonema lectin	Regulation of the ROS-p38-p53 pathway	Melanoma	80
Capsaicin	Increasing ULK1 acetylation and promotion of ROS-dependent autophagy	Melanoma	81
(+)-Bornyl p-coumarate	Upregulation of the expression of Beclin 1, ATG3, ATG5, p62, LC3-I, and LC3-II proteins	Melanoma	82
1,25(OH)2D3	Increased DDIT4 expression and inhibition of mTORC1 activity to promote autophagy	Squamous cell carcinoma	83
Lycopene	Increased levels of the autophagy protein p62, causing Keap1 to be degraded through an autophagy-lysosomal pathway	Cutaneous tumor	84
Vanillic acid	Induction of STAT3-mediated autophagy	Melanoma	85
Honokiol	Activation of LC3B	Melanoma	86
Nitidine chloride	Inhibition of the mTOR pathway	Melanoma	87
Isokotomolide A	Formation of autophagic vacuoles	Melanoma	88
Secokotomolide A	Formation of autophagic vacuoles	Melanoma	88
Gracillin	Suppression of phosphorylation/activation of PI3K, Akt, and mTOR	Melanoma	89
Hibiscus leaf polyphenolic (HLP) extract	Increased expression of ATG5, Beclin 1, and LC3-II	Melanoma	90
Diethyl ether (Et2O) fraction of Jasione montana extract	Induction of autophagy	Melanoma	91
Natto	Formation of acidic autophagic vacuoles and autophagolysosomes	Melanoma	92
East Indian sandalwood oil	Activation of LC3B	Skin cancer	93
Chinese propolis	Decreased ratio of LC3-I/LC3-II and amplification of ATG5/ATG12 complex and p62 protein	Melanoma	94
Ibrutinib	Induction of autophagy and inhibition of cell proliferation by concentration and time-dependent manner	Skin cancer	95
Novel binuclear palladium metallacycle complex with 1,2-bis(dipenylphosphino)ethane	Increased levels of LC3-II and Beclin 1	Melanoma	96
Terfenadine	Promotion of autophagy in both ROS-independent and ROS-dependent manner	Melanoma	97
Bortezomib	Breakdown of LC3 and autophagic formation	Melanoma	98
Triclosan	Through the AMPK/p62/LC3 pathway	Melanoma	99
Neratinib and entinostat combination	ROS-dependent activation of ATM via AMPK-ULK1-ATG13-Beclin 1/ATG5	Melanoma	100
Monobenzone	Induction of tyrosinase ubiquitination and the autophagocytic degradation of melanosomes	Melanoma	101
BAY 87-2243	Promotion of autophagosome formation and mitophagy	Melanoma	102
HA15	Increased ER stress, causing the induction of autophagy	Melanoma	103
Flavonoid GL-V9	Blockage of the Akt/mTOR pathway	Squamous cell carcinoma	104
Lapatinib	Inhibition of the PI3K/Akt/mTOR signaling pathway	Squamous cell carcinoma	105
Temozolomide	Induction of autophagy	Melanoma	1
Dacarbazine	Induction of autophagy	Melanoma	1
Dacarbazine and pitavastatin combination	Increased LC3-II expression	Melanoma	106
Ag/ZnO nanoparticles	Induction of autophagy in response to oxidative stress caused by nanoparticles	Melanoma	107
Nitrogen-doped titanium dioxide nanoparticles	Induction of autophagy in the dark and inhibiting autophagy in the light	Melanoma	108
Nitrogen-phosphorous-doped carbon dot	Upregulation of the protein expression levels of LC3-II and ATG-5	Melanoma	109
Pheophorbide a	Increased expression of the ATGs Beclin 1, LC3B, and ATG5	Melanoma	110
Berberine	Increased level of LC3-related autophagy	Melanoma	111
2-Deoxy-d-glucose	Mitochondria hyperpolarization	Melanoma	112
Pyrimethamine	Increased autophagosome and LC3-II expression	Melanoma	113
Metformin	Regulation of LC3 and Beclin 1 proteins	Melanoma	114
Ivermectin	ROS generation	Melanoma	115
AC-1001-H3	ROS generation and increased LC3/LC3-II and Beclin 1 expression	Melanoma	116
Pyr-1	Enhanced Akt-dependent autophagy	Melanoma	117
Protoapigenone 1′-O-butyl ether	ROS generation	Melanoma	65
Rapamycin	Inhibition of the mTOR pathway and increased Bcl-2, Bax, and LC3-II expressions	Melanoma	118
Hydroxychloroquine	Inhibition of autophagy by preventing the fusion of autophagosomes with lysosomes	Melanoma	119
Hydroxychloroquine and temsirolimus	Concomitant inhibition of mTOR and autophagy	Melanoma	106
Climacostol	Inhibition of autophagy by increasing p53 protein levels and activating AMPKα	Melanoma	120
Decursinol angelate	Inhibition of autophagy by decreasing ATG5, ATG7, Beclin 1, and LC3-II expressions	Melanoma	121
Pinocembrin (5,7-dihydroxy flavanone)	Inhibition of autophagy via activating the PI3K/Akt/mTOR pathway	Melanoma	122
Chloroquine	Modification of mTOR-mediated autophagy, causing the inhibition of autophagy	Melanoma	123
Bafilomycin A1 and ammonium chloride combination	Activation of the p38 MAPK and autophagy inhibition	Melanoma	124
3-Methyladenine and 5-fluorouracil	Inhibition of the LC3 gene in cancer cells	Squamous cell carcinoma	125
Analog of photoactive NADPH NS1	Selective modification of autophagosome formation and autophagy inhibition at the late stage	Melanoma	126
Esomeprazole	Increased accumulation of LC3-II and autophagy inhibition	Melanoma	127
Mibefradil and pimozide	Increased LC3-II/I ratio, accumulation of p62/SQSTM1, and autophagy inhibition	Melanoma	128
Sorafenib	Inhibition of autophagy	Melanoma	1
Sorafenib + α-mangostin	α-Mangostin enhances the activity of sorafenib	NRAS-mutant melanoma	129

Akt: Protein kinase B; AMPK: Adenosine monophosphate-activated protein kinase; ATG: Autophagy-related gene; ATM: Ataxia telangiectasia mutated; DDIT4: Deoxyribonucleic acid damage-inducible transcript 4; ECG: Epicatechin gallate; ER: Endoplasmic reticulum; Et₂O: Diethyl ether; HLP: Hibiscus leaf polyphenolic; IGF-1R: Insulin-like growth factor 1 receptor; JAK: Janus kinase; LC3: Light chain 3; MAPK: Mitogen-activated protein kinase; MITF: Microphthalmia-associated transcription factor; mTOR: Mammalian target of rapamycin; mTORC1: Mammalian target of rapamycin complex 1; NADPH: Nicotinamide adenine dinucleotide phosphate; NF-κB: Nuclear factor kappa B; NRAS: Neuroblastoma RAS viral oncogene homolog; p70S6K: p70 ribosomal S6 kinase; PI3K: Phosphoinositide 3-kinase; ROS: Reactive oxygen species; STAT3: Signal transducer and activator of transcription 3; ULK1: Unc-51-like autophagy-activating kinase 1.