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Dihydroartemisinin accelerates c-MYC oncoprotein degradation and induces apoptosis in c-MYC-overexpressing tumor cells
Lu J.-J.2; Meng L.-H.2; Shankavaram U.T.3; Zhu C.-H.2; Tong L.-J.2; Chen G.2; Lin L.-P.2; Weinstein J.N.1; Ding J.2
2010-07-01
Source PublicationBiochemical Pharmacology
ISSN00062952
Volume80Issue:1Pages:22-30
Abstract

Artemisinin and its derivatives (ARTs) are effective antimalarial drugs and also possess profound anticancer activity. However, the mechanism accounted for its distinctive activity in tumor cells remains unelucidated. We computed Pair wise Pearson correlation coefficients to identify genes that show significant correlation with ARTs activity in NCI-55 cell lines using data obtained from studies with HG-U133A Affymetrix chip. We found c-myc is one of the genes that showed the highest positive correlation coefficients among the probe sets analyzed (r=0.585, P<0.001). Dihydroartemisinin (DHA), the main active metabolite of ARTs, induced significant apoptosis in HL-60 and HCT116 cells that express high levels of c-MYC. Stable knockdown of c-myc abrogated DHA-induced apoptosis in HCT116 cells. Conversely, forced expression of c-myc in NIH3T3 cells sensitized these cells to DHA-induced apoptosis. Interestingly, DHA irreversibly down-regulated the protein level of c-MYC in DHA-sensitive HCT116 cells, which is consistent to persistent G1 phase arrest induced by DHA. Further studies demonstrated that DHA accelerated the degradation of c-MYC protein and this process was blocked by pretreatment with the proteasome inhibitor MG-132 or GSK 3β inhibitor LiCl in HCT116 cells. Taken together, ARTs might be useful in the treatment of c-MYC-overexpressing tumors. We also suggest that c-MYC may potentially be a biomarker candidate for prediction of the antitumor efficacies of ARTs. © 2010 Elsevier Inc.

KeywordApoptosis C-myc Dihydroartemisinin Gsk 3β Nci-60
DOI10.1016/j.bcp.2010.02.016
URLView the original
Indexed BySCI
WOS Research AreaPharmacology & Pharmacy
WOS SubjectPharmacology & Pharmacy
WOS IDWOS:000277497600003
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Cited Times [WOS]:57   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.University of Texas MD Anderson Cancer Center
2.Shanghai Institute of Materia Medica, Chinese Academy of Sciences
3.National Cancer Institute
Recommended Citation
GB/T 7714
Lu J.-J.,Meng L.-H.,Shankavaram U.T.,et al. Dihydroartemisinin accelerates c-MYC oncoprotein degradation and induces apoptosis in c-MYC-overexpressing tumor cells[J]. Biochemical Pharmacology,2010,80(1):22-30.
APA Lu J.-J..,Meng L.-H..,Shankavaram U.T..,Zhu C.-H..,Tong L.-J..,...&Ding J..(2010).Dihydroartemisinin accelerates c-MYC oncoprotein degradation and induces apoptosis in c-MYC-overexpressing tumor cells.Biochemical Pharmacology,80(1),22-30.
MLA Lu J.-J.,et al."Dihydroartemisinin accelerates c-MYC oncoprotein degradation and induces apoptosis in c-MYC-overexpressing tumor cells".Biochemical Pharmacology 80.1(2010):22-30.
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