Table 4.

Autophagy-related medications for osteosarcoma

Drug	Application Status	Target	Tumor Type	Autophagy Activity	Mechanism	Reference
LY294002	Preclinical	PI3K	OS	Inhibitor	Inhibiting PI3K, increasing chemosensitivity in combination with cisplatin	[193]
3-MA	Preclinical	PI3K-III, PI3K-I	OS	Inhibitor	Transient inhibition of PI3K-III and permanent inhibition of PI3K-I, improving OS cell sensitivity to chemotherapy	[193,194]
Wortmannin	Preclinical	PI3KIII, PI3K-I	OS	Inhibitor	Permanently inhibiting PI3KIII and transiently inhibits PI3K-I, also affects mTOR	[193]
NSC185058	Preclinical	ATG4B	OS	Inhibitor	Suppressing LC3 lipidation, inhibits autophagy in OS cells in vivo, suppresses tumor growth	[196]
NSC377071	Preclinical	ATG4B	OS	Inhibitor	May suppress ATG4B activity by regulating the mTOR pathway or PI3K pathway down-regulation	[196]
Chloroquine (CQ)	Preclinical	Autophagosomes and lysosomes	OS	Inhibitor	Deacidifies and blocks the fusion of autophagosomes with lysosomes, triggering lysosomal lysis and cell death	[195,196]
Hydroxychloroquine (HCQ)	Preclinical	Autophagosomes and lysosomes	OS	Inhibitor	Similar to CQ, interferes with critical biological processes independent of autophagy	[195,196]
Spautin-1	Preclinical	VPS34	OS	Inhibitor	Enhancing degradation of VPS34 complexes, synergistic anti-tumor effects with rapamycin	[197]
SAR405	Preclinical	VPS34	OS	Inhibitor	Potently inhibiting VPS34, enhances celecoxib-mediated suppression of cell viability	[198]
Verteporfin	Preclinical	Multiple levels of autophagy	OS	Inhibitor	Disrupting early autophagic processes, induces lysosomal instability, inhibits autophagic flux	[199]
Bafilomycin A1	Preclinical	Lysosomal acidification	OS	Inhibitor	Inhibiting lysosomal acidification, combined with other inhibitors shows cytotoxic effects in OS cells	[200]
NBDHEX	Preclinical	JNK activation	OS	Inhibitor	Triggering autophagic impairment and cell death by JNK activation	[201]
MC3181	Preclinical	JNK activation	OS	Inhibitor	Similar to NBDHEX, triggers autophagic impairment and cell death	[201]
EGCG	Preclinical	p38/MAPK, PI3K/AKT	OS	Inducer	Inhibiting DOX-induced pro-survival autophagy, partially inhibits self-renewal capacity of OSCs	[202,203]
Rapamycin	Preclinical	mTORC1	OS	Inducer	Forms complex with FKBP12, resulting in RAPTOR dissociation and mTORC1 inactivation	[204]
Temsirolimus	Preclinical	mTORC1	OS	Inducer	Water-soluble analog of rapamycin, increases tumor autophagy and reduces tumor growth	[205]
Metformin	Preclinical	AMPK activation	OS	Inducer	Indirectly activating AMPK, promoting inactivation of mTORC1 Complex	[206]
PF-06409577	Preclinical	AMPK subunits	OS	Inducer	Binds selectively to AMPK subunits, more potent effects than traditional activators	[207]
Oridonin	Preclinical	p38 MAPK, JNK, PPAR-γ, Akt, Nrf2 pathways	OS	Inducer	Inducing mitochondria-mediated apoptosis, ROS production, inhibits Akt and Nrf2, activates p38 MAPK, JNK, and PPAR-γ	[208-210]
Wogonin	Preclinical	ROS, STAT3, PRX5	OS	Inducer	Inducing ROS production leading to apoptosis, inhibits STAT3 and PRX5, affects MMP-9 expression in CSCs	[211-213]
Oleuropein	Preclinical	Not specified	OS	Implied	Anti-proliferative properties, role in autophagy induction unclear, used in combination therapy	[214-216]
Evodiamine	Preclinical	PTEN/PI3K/Akt, Wnt/β-catenin	OS	Not specified	Inducing mitochondrial apoptosis, cell-cycle arrest, inactivates PTEN/PI3K/Akt and Wnt/β-catenin pathways	[217-219]
Parthenolide	Preclinical	NF-κB, JNK, ROS	OS	Inducer	Suppressing NF-κB, activates JNK, induces caspase-independent cell death and autophagy via ROS production	[220-222]
Shikonin	Preclinical	ROS, ERK, RIP1, RIP3	OS	Not specified	Inducing apoptosis and necroptosis, increases ROS and activates ERK, suppresses MMP13, enhances effects of doxorubicin	[223,224]
Berberine	Preclinical	MMP2, p53, MAPK signaling	OS	Not specified	Inhibiting cell proliferation, migration, and colony formation, induces cell-cycle arrest and apoptosis, enhances effects of cisplatin	[225-227]
Triptolide	Preclinical	Fas/FasL, caspases, Wnt/β-catenin, DUSP1	OS	Inducer	Reducing cell viability, induces apoptosis and autophagy, suppresses angiogenesis, enhances sensitivity to chemotherapy	[228-230]