Unraveling the Janus-Faced Role of Autophagy in Hepatocellular Carcinoma: Implications for Therapeutic Interventions
Abstract
:1. Introduction
2. Mechanism of Autophagy
3. Autophagy-Regulating Signaling Pathways in HCC
3.1. PI3K/AKT/mTOR
3.2. AMPK/mTOR
3.3. The MAPK (JNK, p38 and ERK)
3.4. Nrf2-p62 Pathway
3.5. Crosstalks between These Pathways
4. Dual Role of Autophagy in HCC
4.1. Autophagy Inhibits HCC Progression
4.2. Autophagy Promotes HCC Progression
4.3. Autophagy in Drug Resistance
5. Selective Autophagy in HCC
5.1. Mitophagy in HCC
5.2. Other Selective Autophagy in HCC
6. The Agents That Target Autophagy in HCC Treatment
6.1. Autophagy Inhibitors
6.2. Autophagy Activators
Compounds | Autophagy Modulators | Experimental Objects | Mechanism |
---|---|---|---|
CQ | Inhibitor | HCC cell line: HepG2 [241] | Lysosomal Inhibitor |
HCQ | Inhibitor | HCC cell lines: HepG2 and Huh7 [242] | |
BafA1 | Inhibitor | Rat liver cell line H-4-II-E [203] | V-ATPase Inhibitor |
HCC cell lines: (BEL7402, LO2, SMMC-7721, Huh7, and HepG2) [204] | |||
3-methyladenine plus delphinidin | Inhibitor | HCC cell line: SMMC7721 [209] | PI3K Inhibitors |
LY294002 | Inhibitor | Normal liver cell line: HL-7702 [210] HCC cell lines: SMMC-7721, BEL-7401, SK-Hep-1 and HEP-G2 [210] | |
VPS34-IN-1 | Inhibitor | HCC cell line: Huh7, MHCC-97H [217] | VPS34 Inhibitor |
MRT68921 plus Cinobufagin | Inhibitor | HCC cell line: HepG2 and Huh7 [221] | ULK1/2 Inhibitor |
SBI-0206965 | Inhibitor | Normal human liver cells (L02) [227] Nutrient-starved human HCC [227] | |
DC-ATG4in | Inhibitor | HCC cell lines: Huh7 and SK-HEP-1 [230] | ATG4B Inhibitor |
Temsirolimus plus Sorafenib | Activator | HCC patients [238] | mTOR inhibitor |
Everolimus plus Sorafenib | Activator | HCC patients [239] |
7. Future Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Nguyen, T.H.; Nguyen, T.M.; Ngoc, D.T.M.; You, T.; Park, M.K.; Lee, C.H. Unraveling the Janus-Faced Role of Autophagy in Hepatocellular Carcinoma: Implications for Therapeutic Interventions. Int. J. Mol. Sci. 2023, 24, 16255. https://doi.org/10.3390/ijms242216255
Nguyen TH, Nguyen TM, Ngoc DTM, You T, Park MK, Lee CH. Unraveling the Janus-Faced Role of Autophagy in Hepatocellular Carcinoma: Implications for Therapeutic Interventions. International Journal of Molecular Sciences. 2023; 24(22):16255. https://doi.org/10.3390/ijms242216255
Chicago/Turabian StyleNguyen, Thi Ha, Tuan Minh Nguyen, Dinh Thi Minh Ngoc, Taesik You, Mi Kyung Park, and Chang Hoon Lee. 2023. "Unraveling the Janus-Faced Role of Autophagy in Hepatocellular Carcinoma: Implications for Therapeutic Interventions" International Journal of Molecular Sciences 24, no. 22: 16255. https://doi.org/10.3390/ijms242216255