Table 2.

Effects of artemisinins and its derivatives on cell proliferation, tumour growth, invasion and metastasis.

	Disease model	Cell line(s)/ stimulus/ allergen/ animal type	Derivative	Effective conc./ dose; route of administration	Outcomes	Ref.
invitro	Asthma	ASM	Artesunate	3−30 μM	↓ cell number, p-Akt, p-p70S6K, cyclin D1	[31]
	Lung cancer	A549	Artemisinin	250−1000 μM	↓ colony formation	[20]
			Artesunate	100−150 μM
		A549	DHA	10−60 μM	↓ colony formation	[21]
		PC-9		8−64 μM
		A549, H1299	DHA/ Arteminsinin/ Artesunate	7.5−30 μM	↓ cyclin D1, Wnt5-a/b, LRP6, Dvl2, β-catenin, invasion, migration, EMT, CSCs; ↑ G1 phase cell cycle arrest, NKD2, Axin2	[22]
		A549	DHA	10−30 μM	↑ sub-G1 and G1 phase cell cycle arrest, p21; ↓ cyclin D1, PCNA, p-Akt, p-GSK3β	[23]
		A549	DHA	3.2−1000 nmol/L	↑ population doubling time, G0/G1 phase cell cycle arrest	[24]
		PC-14	DHA	5−320 μM	↓ cell proliferation	[25]
		ASTC-a-1	DHA	1−30 μg/mL	↓ cell proliferation	[28]
		A549, NCI-H661, SK-MES-1, Spc-A-1	DHA	2.5 μM	↓ IC50; Chemosensitize with onconase	[29]
		A549	Artesunate	10−20 μg/L	↓ cell proliferation, invasion	[30]
		A549	Artesunate	75 μM	↑ sub-G1 population; Chemosensitize with 50 μM CQ	[33]
			DLAe	50 μM	↑ G2/M, p-H2AX; ↓ migration	[34]
		H1299	DLAe	50−75 μM	↑ G2/M, p-H2AX	[34]
		A549	DLAe	100−150 μM	↑ G1, p-H2AX; ↓ migration	[34]
		A549	Compound 17	0.2−30 μM	↓ cell proliferation	[35]
		LLC	DHA	10−40 μg/mL	Chemosensitize with 25 μg/mL carboplatin	[36]
		GLC-82	DHA	4−128 μg/mL	↑ G0/G1 phase cell cycle arrest; ↓ S phase; Promote radiosensitization	[37]
		H1975	DHA	10 μM	↓ cyclin B1 and CDK1, migration and invasion; Chemosensitize with 10 μM gefitinib	[38]
		A549	DHA	10−30 μg/mL	↑ G2/M phase cell cycle arrest; Synergistic with low-dose ionising radiation (2 or 4 Gy)	[39]
		A549	Artesunate	50−1600 μM	↑ NO, G2/M phase cell cycle arrest; ↓ cyclin B1 and cdc2 mRNA; Radiosensitize with local radiotherapy	[40]
		A549	Artesunate	1−100 μM	No ↓ in cell viability, ↓ cyclin D, CDK4, p-Rb; blockade at all cell cycle phases; Chemosensitize with 0.1−1 μM lentilomide	[42]
		HCT116	Artesunate	1−100 μM	↓ cell viability, cyclin D, CDK4, p-Rb; ↑ sub-G1, p21	[42]
		MCF7	Artesunate	1−100 μM	No ↓ in cell viability, ↓ cyclin D, CDK4, p-Rb; ↑ p21; blockade at all cell cycle phases (>30 μM), ↑ G1 and ↓ S phase (<30 μM); Chemosensitize with 0.1−1 μM lentilomide	[42]
		H1975	DHA	15 μM	Chemosensitize with 2 μM ABT-263	[48]
		LLC	DHA	20−80 μmol/L	↓ cell proliferation	[49]
		H460, H1299, Calu3, LXF289, A549, H1398	Artesunate	2.5 μM	↓ cell proliferation, AP-1 activity, matrigel invasion	[54]
		A549, H1975	DHA	7.5−30 μM	↓ cyclin D1, migration and invasion	[55]
		A549	DHA	0.71−11.36 mg/L (A549) 1.42−22.72 mg/L (A549/DDP)	Chemosensitize with 0.46875−7.5 mg/L (A549) or 0.9375−15 mg/L (A549/DDP) cisplatin	[56]
		A549	ARTD	2.5−7.5 μM	↓ cell proliferation, E2F1, migration and invasion	[58]
		A549	DHA	10 μg/mL	Chemosensitize with 10 μg/mL doxorubicin	[59]
		A549, ASTC-a-1	DHA	20 μg/mL	Chemosensitize with 1−20 μM JNK inhibitor SP600125	[60]
		A549	DHA	6−12 μg/mL	Chemosensitize with 100−500 μM dictamine	[61]
		A549	DHA	30−90 μM	↓ S phase; ↑ G2/M phase cell cycle arrest in combination; Chemosensitize with 10−60 μM arsenic trioxide	[62]
		A549	DHA	10−20 μg/mL	↑ G2/M and sub-G1 phase cell cycle arrest; ↓ G0/G1 arrest; Chemosensitize with 1−10 μg/mL gemcitabine	[63]
		ASTC-a-1, 95D, H446	DHA	5−40 μg/mL	↓ cell proliferation; Chemosensitize with 1−10 μg/mL gemcitabine	[63]
		A549	Artesunate	25–100 μM	↓ cell proliferation	[83]
	SCLC	H69, H69VP	Artemisinin	2−20 nM	Pre-treatment with 880 nM transferrin ↓ IC50	[64]
	EMT	TGFβ1-induced EMT RLE-6TN	Artesunate	n.d.	↓ EMT	[82]
	HCMV	HCMV infection in HELF	Artesunate	12.5−400 μM	↓ NF-κB, Sp1, p-Akt1, p-p70S6K	[32]
	ALI	LPS-induced ALI in A549	Artesunate	1−4 μM	No change	[52]
	Nasopharyngeal carcinoma	C666−1, HONE-1, HK1, HNE1, CNE2	Artesunate	10−40 μM	↑ G2/M phase cell cycle arrest, cyclin B1, p-Akt, p-mTOR, p-4EBP1; ↓ Rb, E2F-1; Chemosensitize with 10 μM cisplatin	[41]
in vivo	Lung cancer	A549; nude mice	DHA/ Artemisinin/ Artesunate	60 mg/kg/day; gavage	↓ tumour growth, β-catenin, oct3/4, sox2, nanog, vimentin, Wnt5-a/b, LRP6, Dvl2; ↑ NKD2, Axin2	[22]
		A549; nude mice	DHA	100 mg/kg/day; oral gavage	↓ tumour growth	[24]
		A549; BALB/c nude mice	DHA	10 mg/kg; i.p.	↓, chemosensitize with 3 mg/kg onconase	[29]
		A549; nu/nu mice	DLAe	85 mg/kg; p.o. gavage	↓ tumour growth	[34]
		A549; nude mice	Artesunate	7.5−30 mg/kg once; i.m.	Combination with local radiotherapy ↓ tumour growth	[40]
		H1975; nude mice	DHA ABT-263	25 mg/kg 100 mg/kg/day; oral gavage	Combination therapy ↓ tumour growth by >51 %	[48]
		LLC; C57BL/6 mice	DHA	50−100 mg/kg/day; i.g.	↓ tumour growth; Chemosensitize with 50 mg/kg/day CTX to ↓ pulmonary metastasis	[49]
		A549; BALB/c mice	DHA	50−200 mg/kg/day; i.g.	↓ tumour growth; Chemosensitize with 2 mg/kg/day CDDP	[49]
		A549; nude mice	DHA	50−100 mg/kg/day	↓ metastasis	[55]
		LLC; C57BL/6 mice	Artemisinin	50 mg/kg/day; orally	No change in tumour growth; ↓ lung metastatic nodules, lymph node metastases	[57]
		A549; BALB/c mice and ovariectomized mice	ARTD	10−20 mg/kg; oral gavage	↓ cancer-associated bone metastasis, E2F1; ↑ ATF3	[58]
		A549; BALB/c athymic nude mice	Artesunate	60−120 mg/kg/day; oral gavage	↓ p-EGFR, p-Akt, Akt, ABCG2	[83]
	Metastasis assay	H460; chicken embryo	Artesunate	i.v.	↓ tumour growth and metastasis	[54]
	NSCLC	120 advance stage patients	Artesunate	120 mg/day; i.v.	Chemosensitize with vinorelbine and cisplatin therapy to ↑ time to progression, and disease controlled rate	[84]
	NPC	C666−1 or CNE2; SCID mice	Artesunate	100 mg/kg/day; i.p.	↓ tumour growth; Synergistic with 40 mg/kg/day cisplatin	[41]

n.d.: no data.