. 2020 May 13;158:104901. doi: 10.1016/j.phrs.2020.104901

Table 3.

Effects of artemisinins and its derivatives on apoptosis.

	Disease model	Cell line(s)/ stimulus/ allergen/ animal type	Derivative	Effective conc./ dose; route of administration	Outcomes	Ref.
invitro	Lung cancer	A549	Artemisinin	250-1000 μM	↑ cell death, LDH, ROS, DNA damage	[20]
		A549	Artesunate	100-150 μM	↑ cell death, LDH, ROS, DNA damage	[20]
		A549	DHA	10−60 μM	↑ ROS, caspases 3, 8 and 9, cytochrome c and AIF when synergize with 2DG	[21]
		PC-9	DHA	8−64 μM		[21]
		A549	DHA	10−30 μM	↑ Bax, caspase 3, cytochrome c; ↓ Bcl-2	[23]
		PC-14	DHA	5−320 μM	↑ [Ca²⁺]_i, p-p38	[25]
		ASTC-a-1	Artemisinin	200−500 μM	↑ ROS, caspases 3, 8 and 9	[26,27]
		ASTC-a-1	DHA	1−30 μg/mL	↑ change in mitochondrial morphology, caspase 3; ↓ ΔΨm	[28]
		A549, NCI-H661, SK-MES-1, Spc-A-1	DHA	2.5 μM	↓ endothelial tube formation	[29]
		A549	Artesunate	75 μM	↑ ROS, cytochrome c, and cleaved caspase 3	[33]
			DLAe	50 μM	↑ caspases 3, 8 and 9	[34]
		H1299	DLAe	50−75 μM	↑ caspases 3, 8 and 9	[34]
		A549	DLAe	100−150 μM	↑ caspases 3, 8 and 9	[34]
		A549	Compound 17	0.2−30 μM	↑ ROS	[35]
		LLC	DHA	10−40 μg/mL	↑ p-p38	[36]
		GLC-82	DHA	4−128 μg/mL	↑ p53, p21; ↓ Bcl-2	[37]
		H1975	DHA	10 μM	↓ p-Akt, p-mTOR, p-STAT3, and Bcl-2; ↑ Bax	[38]
		A549	DHA	10−30 μg/mL	↑ ROS, caspases 3, 8 and 9, tBid translocation, Bax; ↓ Bcl-xL	[39]
		A549	Artesunate	50−1600 μM	No effect	[40]
		ASTC-a-1	DHA	20 μg/mL	↑ ROS, Bax translocation, change in mitochondrial morphology, cytochrome c, caspases 3, 8 and 9; ↓ ΔΨm	[43]
		A549, ASTC-a-1	Artesunate	10−50 μg/mL	↑ ROS, Smac, AIF, caspase 3, Bak; ↓ ΔΨm	[44]
		A549	Artemisinin	400 μM	↑ ROS, caspases 3, 8 and 9, Bak, Smac, AIF	[45]
		A549, ASTC-a-1	DHA	20 μg/mL	↑ Bim, Bim translocation	[46]
		SPC-A-1	DHA	30 μM	↑ [Ca²⁺]_i; ↓ survivin	[47]
		H1975	DHA	15 μM	↓ p-STAT3, Mcl-1, and inflammation; ↑ Bim	[48]
		LLC	DHA	20−80 μmol/L	↑ chromatin condensation, shrunken nucleus; ↓ KDR/flk-1	[49]
		H460, H1299, Calu3, LXF289, A549, H1398	Artesunate	2.5 μM	↓ AP-1 activity	[54]
		A549, H1975	DHA	7.5−30 μM	↓ Bcl2, XIAP	[55]
		A549	DHA	0.71−11.36 mg/L (A549) 1.42−22.72 mg/L (A549/DDP)	↓ HIP-1α, VEGF	[56]
		A549, ASTC-a-1	DHA	20 μg/mL	↑ Bax translocation, cytochrome c release, and caspases 3 and 9; ↓ ΔΨm	[60]
		A549	DHA	6−12 μg/mL	caspase 3-dependent	[61]
		A549	DHA	30−90 μM	↑ ROS, DNA damage	[62]
		A549	DHA	10−20 μg/mL	↑ ROS, Bak, caspases 3, 8 and 9, tBid; ↓ ΔΨm	[63]
		ASTC-a-1, 95D, H446	DHA	5−40 μg/mL	↑ apoptosis	[63]
		A549	Artesunate	25–100 μM	↓ p-EGFR, EGFR, p-Akt, ABCG2	[83]
	SCLC	H69, H69VP	Artemisinin	2−20 nM	↑ DNA fragmentation	[64]
	Nasopharyngeal carcinoma	C666−1, HONE-1, HK1, HNE1, CNE2	Artesunate	10−40 μM	↑ caspase 3, cleaved PARP, mitochondrial superoxide, ROS; ↓ oxygen consumption rate, ATP	[41]
in vivo	Lung cancer	H1975; nude mice	DHA	25 mg/kg	↓ p-STAT3, Mcl-1; ↑ Bim	[48]
		H1975; nude mice	ABT-263	100 mg/kg/day; oral gavage	↓ p-STAT3, Mcl-1; ↑ Bim	[48]
		A549 and A549/DDP; BALB/c athymic mice	DHA	50, 100, 200 mg/kg/day; i.g.	↑ apoptosis	[56]
		A549 and A549/DDP; BALB/c athymic mice	Cisplatin	2 mg/kg/3 days, 12 (A549) or 28 (A54/DDP) days; i.p.	↑ apoptosis	[56]