Table 2.

Mechanisms of HDACi-induced autophagic cell death.

Molecular Mechanism	Additional Mechanism	HDACi	Cell Type	Autophagy Monitoring	Ref.
mTOR Inhibition	S6rp phosphorylation; increased p21 expression	SAHA	ESS-1	GFP-LC3; MDC staining; TEM	[120,171]
	Increase of LC3 expression; activation of ULK-1 complex	SAHA	MEFs, T98G Glioblastoma	p62, LC3-I/-II, ATG3, ATG7 WB; GFP-LC3	[173]
	Beclin-1 upregulation	SAHA, Butyrate	HelaS3	GFP-LC3; AVO; FACS	[170,177]
	Induction of ER stress response	SAHA, OSU-HDAC42	HCC, Hep3B, HepG2	LC3-I/-II WB; GFP-LC3; TEM	[178]
	ROS accumulation via Cat D, repression of TRX; BECN1 and ATG-7 upregulation.	SAHA	Jurkat T-leukemia	BECN1, Atg5, 7, 12 LC3-I/-II WB; GFP-LC3; AVO; TEM	[180]
	BECN1 protein upregulation. and p62 downregulation	SAHA	Gliobastoma stem cells	LC3-I/-II, BECN1, p62 WB; AVO; IF, TEM	[181]
	* CASP and CPN-1 activation; reduced ATG expression	MGCD0103	Primary CLL	p62, LC3-I/-II, ATG5-12; BECN1 WB;	[198]
	Increased ATG5 expression	Apcidin	Salivary MEC	LC3-I/-II, p62 WB; AVO	[209]
ROS Accumulation	CathD upregulation and TRX repression	SAHA	K562, LAMA 84 CMLL	N-acetyl-cysteine, chloroquine	[182]
	Activation of MAPK proteins: ERK1/2 and JNK; LC3 and ATG12 upregulation	FK228 + bortezo-mib	Gastric carcinoma (GC)	LC3-I/-II, Beclin-1, ATG-12 WB	[199]
	p38 MAPK switch to apoptosis; ERK activation	M-275	HCT116	LC3-I/-II ATG5,7 WB; GFP-LC3; TEM	[200]
p21 CIP/WAF1 Upregulation		SAHA, H40	PC-3M, HL-60	MDC staining	[201]
	Downregulation of pERK/NF-κB signaling	MRJF4	PC3	LC3-I/-II WB; TEM	[202]
NF-κB Hyperacetyl-ation	Induction of NF-κB target genes	SAHA, MS-275	PC3	Expr. Profiling/ATGs; LC3-I/-II, p62 WB	[206]
AIF nucleus Translocation		FK228	MRT	LC3-I/-II; LC3 IF; TEM	[205]
Apoptosome Inactivation	Independent of p53; Deletion of Apaf-1/Casp-9	LAQ824, LBH589	Eμ-myc lymphomas	LC3-I/-II WB; TEM	[207]
FoxO1 Transcription	ATG expression; mTOR suppression via SESN3	SAHA, TSA	HepG2, HCT116	LC3, p62 WB; GFP-LC3;	[12]
DAPK Upregulation		LBH589	HCT116	p62 WB; LC3-I/-II WB; LC3 IF; AVO	[176]
ATG7 Acetylation *	Autophagy interactome acetylation; increased mitochondrial mass and ROS formation	SAHA, TSA, LBH589, JQ2	Megakaryo-blastic leukemia	GFP-LC3; mCherry-LC3	[11]
ATG Gene Upregulation *	Independent of p53 acetylation	Tenovin-6	CLL	LC3-I/LC3-II, p62 WB; TEM	[208]
p53 Acetylation	Increased p53-dependent cell cycle arrest and apoptosis	Sirtinol	MCF-7	LC3-I/-II WB; AVO; MDC staining	[203]
	p53 activation. by reducing MDM2 expression; cell cycle arrest and apodosis	MHY2256	MCF-7	LC3-I/-II BECN1 ATG5, 7 WB; AVO	[204]
p53-Deficiency	mTOR inhibition	SAHA	ESS-1	p-mTOR WB; MDC staining, GFP-LC3	[197]

* Leads to inhibition of autophagy; AVO (acidic vesicular organelles).