BioMed Research International / 2012 / Article / Tab 2

Review Article

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

Table 2

Antitumor effects of artemisinins.

CmpdCancer/cell lineEffectEvent/mechanismRefs

DHA/ARTOsteosarcomaGrowth arrestG2/M, decreased survivin[73]
4 cell lines with different p53 statusApoptosisIncreased Bax, activation of caspase 3,8,9
Decreased Bc12, Cdc25B, cyclin B1, NF-κB

DHAHepatoma (different cell lines)Growth arrestG1, decreased cyclin D, E, CDK2-4, E2F1
Increased Cip 1/p21, Kip 1/p27
ApoptosisIncreased Bax/Bcl2 ratio, activation of caspase 3
Increased poly ADP-ribose polymerase
Decreased MDM2

DHA/ARTNeuroblastomaGrowth arrestG1[52]
ApoptosisActivation of caspase 3

DHAPancreas (BxPC3 RFP)Growth arrestG1, decreased cyclin D1, increased p21[74]
ApoptosisIncreased Bax, decreased Bcl2[74, 75]
AngiogenesisDecreased VEGF[75, 76]
Decreased NF-κB DNA binding[74, 76]
IL-8, COX2, MMP9[76]

DHAHuman promyelocyticGrowth arrestG1[33, 34]
Leukemia (HL-60)ApoptosisER stress, degradation of c-MYC[33]
Colorectal cancer (HT116)Increased GRP78[34]
DNA damage[33]

DHALung cancer (SPCA1)ApoptosisDecreased survivin[56]
(PC-14)Increased calcium levels, increased p38 MAPK[57]
(ASTC-a-l)Increased oxidation, activation caspase 3,9,8
Bax translocation

DHA/ARSHuman ovarian cancer (cell panel, A2780, OVCAR-3)Growth arrestG2[69]
ApoptosisIncreased Bax-Bad, decreased Bclx-Bcl2[69, 77]
Activation caspase 3/9 pathway[69, 77]

DHALymphatic endothelial cellsApoptosisIncreased Bax, decreased Bcl2
Decreased VEGFR-3/FL-4

DHAMelanoma (A375, G361, LOX)ApoptosisIncreased oxidative stress, increased NOXA
Activation caspase 3

DHAJurkat T LymphomaApoptosisDNA damage
Increased oxidation, increased NOXA
Increased Bak, activation of caspase 9

DHAFibrosarcoma (HT 1080)Migration/invasionDecreased NF-κB, AP-1
Decreased activation of MMP2, MMP9
Decreased PKC α/Raf/ERK and JNK

DHAGlioma cells (C6)ApoptosisDecreased HIF 1α, VEGF[41]

DHAChronic myeloid leukemia (K562 cells)Growth arrestG2, decreased PCNA, cyclin B1, D1, E1[82]
CDK2-4, E2F1, DNA-PK, DNA-topo1, JNK VEGF[68]

ARTAngiogenesisDecreased VECF[82]

DHALewis lung carcinomaAngiogenesisDecreased VEGF-C, IL-1 β-induced p38 [83]
MAPK activation
Decreased VEGF receptor KDR/flk-1[84]

DHA/ARTCervix carcinoma (HeLa)
Human papillomavirus immortalized/transformed cells
ApoptosisActivation of caspase 9[85]

ARTLeukemia, melanoma,
non-small cell lung cancer,
colon, renal, ovarian, prostate,
CNS; prostate, breast cancer
(NIC cell panel)
Growth arrestG0/G1, decreased CDK2, CDC25A
G2/M, decreased cyclin B1

ARTEndometrial carcinoma (HEC-1B)Growth arrestG0/G1 [86]
ApoptosisActivation of caspase 3, decreased COX-2
AngiogenesisIncreased E-cadherin

ARTPancreatic cancer (BxPC3, MiaPaCa-2)ApoptosisActivation of caspases 3, 7
Inhibition of topoisomerase II a

ARTNon-small cell lung cancer (SPC-A1)MetastasisDecreased MMP2, transactivation of AP-1[56, 88]
uPA promoter[88]

ARTColorectal (CLY, HT29, Lovo)MetastasisIncreased E cadherin
Decreased Wnt-signalling pathway

ARTMouse myeloma cell line SP2/0Growth arrestG0/G1[90]
ApoptosisDecreased NF-κB p65, increased IκBα

ARSHepatocellular cancer cells (HepG2, SMMC-7721)MetastasisIncreased TIMP2, Cdc42, E cadherin [91]
Decreased MMP2
Nasopharyngeal cancer lines (CNE-1 and CNE-2)Growth arrestG1[92]
Melanoma (A375P, A375M)Growth arrest [93]
MigrationDecreased MMP2, αvβ3 integrin

ATMColorectal (HCT116, SW480)Growth arrestG1, 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.