Table 1 Evidence of doxorubicin-induced autophagy in the heart.

Model	Targets	Autophagy	Treatment/Effect on DIC	References
NRCM; C57BL/6J mice	AMPK ↑ LC3-II ↑ Atg 5, 6, 8, 12 ↑	Increase	Ghrelin/ protection; 3-MA/ protection; Compound C/ protection	¹⁷
H9c2; MEFs	AMPK ↓ Sirt1 dysfunction	Decrease	Genetic deletion of AMPK/susceptibility; Resveratrol/ protection	²⁴
C57BL/6J mice; NRCM; H9Cc2	LC3-II ↑ lysosomal cathepsins ↓	Decrease	Beclin 1+/−/protection Beclin 1 overexpression/susceptibility BafA1/ protection	³⁰
SD rats; ARCM; AMCM; NRCM; H9Cc2	TFEB ↓ Cathepsin B ↓	Decrease	TFEB overexpression/protection Torin 1/protection	³³
NRCM	mTOR activation; Beclin 1 inhibition	Decrease	3-MA/ susceptibility; siRNA-Beclin 1/susceptibility; rapamycin/protection	¹²²
H9c2 cells, C57BL/6J mice	Beclin 1 ↑ LC3II/I ↑	Increase	Ophiopogonin-D/protection; 3-MA/protection	¹²³
NRCMs	GATA4 ↓ Bcl-2 ↓ LC3-II ↑ autophagy flux ↑	Increase	3-MA/protection; Rapamycin/susceptibility	¹²⁴
ARVMs	LC3-I, LC3-II ↑ Lysosomal acidification ↓	Decrease	CQ/susceptibility	³²
SD rats; NRCM	Beclin 1 ↑	Increased	3-MA/ protection	¹²⁵
NRCM	Beclin 1 ↑ Atg5 ↑ Atg 12 ↑	Increase	Resveratrol/ protection; 3-MA/ protection; shBeclin 1/ protection	¹²⁶
C57BL/6J mice	Nrf-2 ↑ LC3-I, LC3-II ↑ p62 ↑ Autophagic flux ↓	Decrease	Nrf2-/- / susceptibility Nrf2 overexpression/ protection BafA1/ susceptibility	¹²⁷
SD Rat; NRCM; H9c2	AMPK ↓ mTOR ↑ LC3-II ↓ Autophagic flux ↓	Decrease	Astragalus polysaccharides/ protection	¹²⁸

NRCM neonatal rat cardiomyocytes, ARCM adult rat cardiomyocytes, ARVMs adult rat ventricular myocytes, 3-MA 3-methyl adenine, BafA1 bafilomycin 1, AMCM adult mice cardiomyocytes, TFEB transcription factor EB, Nrf-2 Nuclear factor erythroid 2-related factor 2, LC3-II microtubule-associated protein 1A/1B-light chain 3, Atg autophagy-related protein, CQ chloroquine, SIRT1 Sirtuin 1, DIC doxorubicin-induced cardiotoxicity, MEFs mouse embryonic fibroblasts, SD Sprague Dawley, sh short hairpin RNA; ↓ decrease, ↑ increase.

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