Antitumor Activity of Artemisinin and Its Derivatives: From a Well-Known Antimalarial Agent to a Potential Anticancer Drug

Table 2

Antitumor effects of artemisinins.

Cmpd	Cancer/cell line	Effect	Event/mechanism	Refs
DHA/ART	Osteosarcoma	Growth arrest	G2/M, decreased survivin	[73]
	4 cell lines with different p53 status	Apoptosis	Increased Bax, activation of caspase 3,8,9; Decreased Bc12, Cdc25B, cyclin B1, NF-κB	[44]
DHA	Hepatoma (different cell lines)	Growth arrest	G1, decreased cyclin D, E, CDK2-4, E2F1; Increased Cip 1/p21, Kip 1/p27	[67]
		Apoptosis	Increased Bax/Bcl2 ratio, activation of caspase 3; Increased poly ADP-ribose polymerase; Decreased MDM2
DHA/ART	Neuroblastoma	Growth arrest	G1	[52]
		Apoptosis	Activation of caspase 3
DHA	Pancreas (BxPC3 RFP)	Growth arrest	G1, decreased cyclin D1, increased p21	[74]
		Apoptosis	Increased Bax, decreased Bcl2	[74, 75]
		Angiogenesis	Decreased VEGF	[75, 76]
			Decreased NF-κB DNA binding	[74, 76]
			IL-8, COX2, MMP9	[76]
DHA	Human promyelocytic	Growth arrest	G1	[33, 34]
	Leukemia (HL-60)	Apoptosis	ER stress, degradation of c-MYC	[33]
	Colorectal cancer (HT116)		Increased GRP78	[34]
			DNA damage	[33]
DHA	Lung cancer (SPCA1)	Apoptosis	Decreased survivin	[56]
	(PC-14)		Increased calcium levels, increased p38 MAPK	[57]
	(ASTC-a-l)		Increased oxidation, activation caspase 3,9,8; Bax translocation	[54]
DHA/ARS	Human ovarian cancer (cell panel, A2780, OVCAR-3)	Growth arrest	G2	[69]
		Apoptosis	Increased Bax-Bad, decreased Bclx-Bcl2	[69, 77]
			Activation caspase 3/9 pathway	[69, 77]
DHA	Lymphatic endothelial cells	Apoptosis	Increased Bax, decreased Bcl2; Decreased VEGFR-3/FL-4	[78]
DHA	Melanoma (A375, G361, LOX)	Apoptosis	Increased oxidative stress, increased NOXA; Activation caspase 3	[79]
DHA	Jurkat T Lymphoma	Apoptosis	DNA damage; Increased oxidation, increased NOXA; Increased Bak, activation of caspase 9	[80]
DHA	Fibrosarcoma (HT 1080)	Migration/invasion	Decreased NF-κB, AP-1; Decreased activation of MMP2, MMP9; Decreased PKC α/Raf/ERK and JNK	[81]
DHA	Glioma cells (C6)	Apoptosis	Decreased HIF 1α, VEGF	[41]
DHA	Chronic myeloid leukemia (K562 cells)	Growth arrest	G2, decreased PCNA, cyclin B1, D1, E1	[82]
			CDK2-4, E2F1, DNA-PK, DNA-topo1, JNK VEGF	[68]
ART		Angiogenesis	Decreased VECF	[82]
DHA	Lewis lung carcinoma	Angiogenesis	Decreased VEGF-C, IL-1 β-induced p38	[83]
			MAPK activation
			Decreased VEGF receptor KDR/flk-1	[84]
DHA/ART	Cervix carcinoma (HeLa); Human papillomavirus immortalized/transformed cells	Apoptosis	Activation of caspase 9	[85]
ART	Leukemia, melanoma,; non-small cell lung cancer,; colon, renal, ovarian, prostate,; CNS; prostate, breast cancer; (NIC cell panel)	Growth arrest	G0/G1, decreased CDK2, CDC25A; G2/M, decreased cyclin B1	[5]
ART	Endometrial carcinoma (HEC-1B)	Growth arrest	G0/G1	[86]
		Apoptosis	Activation of caspase 3, decreased COX-2
		Angiogenesis	Increased E-cadherin
ART	Pancreatic cancer (BxPC3, MiaPaCa-2)	Apoptosis	Activation of caspases 3, 7; Inhibition of topoisomerase II a	[87]
ART	Non-small cell lung cancer (SPC-A1)	Metastasis	Decreased MMP2, transactivation of AP-1	[56, 88]
			NF-κB
			uPA promoter	[88]
			MMP7	[56]
ART	Colorectal (CLY, HT29, Lovo)	Metastasis	Increased E cadherin; Decreased Wnt-signalling pathway	[89]
ART	Mouse myeloma cell line SP2/0	Growth arrest	G0/G1	[90]
		Apoptosis	Decreased NF-κB p65, increased IκBα
ARS	Hepatocellular cancer cells (HepG2, SMMC-7721)	Metastasis	Increased TIMP2, Cdc42, E cadherin	[91]
			Decreased MMP2
	Nasopharyngeal cancer lines (CNE-1 and CNE-2)	Growth arrest	G1	[92]
	Melanoma (A375P, A375M)	Growth arrest	—	[93]
		Migration	Decreased MMP2, αvβ3 integrin
ATM	Colorectal (HCT116, SW480)	Growth arrest	G1, S, G2, decreased CDK1	[63]
			All phases
	Breast (MCF-7)		G1, decreased CDK4, cyclin D1

Abbreviations: Cmpd: compound; DHA: Dihydroartemisinin; ART: artesunate, ARS: artemisinin, ATM: artemisone.