Targeting and regulation of autophagy in hepatocellular carcinoma: revisiting the molecular interactions and mechanisms for new therapy approaches

Hashemi, Mehrdad; Nadafzadeh, Niloufar; Imani, Mohammad Hassan; Rajabi, Romina; Ziaolhagh, Setayesh; Bayanzadeh, Seyedeh Delaram; Norouzi, Raheleh; Rafiei, Reihaneh; Koohpar, Zeinab Khazaei; Raei, Behnaz; Zandieh, Mohammad Arad; Salimimoghadam, Shokooh; Entezari, Maliheh; Taheriazam, Afshin; Alexiou, Athanasios; Papadakis, Marios; Tan, Shing Cheng

doi:10.1186/s12964-023-01053-z

Cell Communication and Signaling

Table 3 Use of anticancer compounds for targeting autophagy in HCC treatment

From: Targeting and regulation of autophagy in hepatocellular carcinoma: revisiting the molecular interactions and mechanisms for new therapy approaches

Anticancer compound	Molecular pathway	Remark	Ref
Sterodial saponins	LC3-II p62	Sterodial saponins increase LC3- II and p62 levels, indicating their role in impairing autophagy flux and reducing tumor growth	[251]
Quercetin	Akt/mTOR	Quercetin inhibits Akt/mTOR axis to induce autophagy and mediate apoptosis	[252]
Propyl gallate	-	Increasing the conversion of LC3-I to LC3- II and triggering autophagy in reducing HCC progression	[253]
Lycorine	TCPR1/Akt/mTOR	Lycorine suppresses the TCPR1/Akt/mTOR axis in triggering autophagy and apoptosis	[254]
Exenatide	mTOR	Exenatide suppresses the mTOR pathway in triggering apoptosis and autophagy	[255]
Astragaloside II	MAPK/mTOR	Astragaloside II suppresses autophagy and increases sensitivity to 5-fluorouracil Induction of MAPK/mTOR signaling	[256]
Metformin	AMPK	Metformin increases sorafenib sensitivity of HCC cells via autophagy induction in an AMPK-dependent manner	[257]
Regorafenib	Akt/mTOR	Regorafenib suppresses the Akt/mTOR axis by inducing autophagy and reducing tumor cell growth rate	[258]
4-phenoxyphenol derivative, 4-[4-(4-hydroxyphenoxy)phenoxy]phenol (4-HPPP)	α-tubulin	4-HPPP reduces α-tubulin expression and induces apoptosis and autophagy	[259]
Wogonin Sorafenib	–	Combination of wogonin and sorafenib induces apoptosis and suppresses autophagy to reduce tumor progression	[260]
ABT-737	Beclin-1	ABT-737 induces autophagy via ROS and upregulation of Beclin-1 Pro-survival function of autophagy	[261]
3-methyladenine	–	Inhibition of autophagy in enhancing sorafenib sensitivity of cancer cells	[262]
Cardiac glycosides	AMPK	Autophagy induction by AMPK upregulation Autophagy inhibition increases capacity for apoptosis induction	[263]
Morin hydrate	PARP1/HMGB1	Morin hydrate suppresses PARP1/HMGB1 axis in autophagy inhibition and suppresses cisplatin resistance	[264]
Chloroquine	–	Chloroquine suppresses autophagy and prevents mitochondrial dysfunction in promoting chemosensitivity	[265]
GL-V9	JNK2	GL-V9 suppresses autophagy via downregulation of JNK2 in reversing adriamycin resistance	[266]

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