Triptolide-induced apoptosis by inactivating nuclear factor-kappa B apoptotic pathway in multiple myeloma in vitro

Rong Zeng , Linlan Zeng , Yan Chen , Fei Zhao , Rui Li , Lu Wen , Chun Zhang

Current Medical Science ›› 2011, Vol. 31 ›› Issue (4) : 446 -451.

PDF
Current Medical Science ›› 2011, Vol. 31 ›› Issue (4) : 446 -451. DOI: 10.1007/s11596-011-0471-7
Article

Triptolide-induced apoptosis by inactivating nuclear factor-kappa B apoptotic pathway in multiple myeloma in vitro

Author information +
History +
PDF

Abstract

The effect of triptolide on proliferation and apoptosis of human multiple myeloma RPMI-8226 cells in vitro, as well as the roles of nuclear factor-kappa B (NF-κB) and IκBα was investigated. The effect of tritptolide on the growth of RPMI-8226 cells was studied by MTT assay. Apoptosis was detected by Hoechest 33258 staining and Annexin V/PI double staining assay. The expression of NF-κB and IκBα was observed by Western blot and confocal microscopy. The results showed that triptolide inactivated NF-κB apoptotic pathway in human multiple myeloma RPMI-8226 cells. Triptolide at nM range induced proliferation inhibition in a dose- and time-dependent manner and apoptosis in a dose-dependent fashion in RPMI-8226 cells. Besides, we observed the inhibition of NF-κB /p65 in the nuclear fraction was correlated with the increase in the protein expression of IκBα in the cytosol. These results suggested that triptolide might exhibit its strong anti-tumor effects via inactivation of NF-κB/p65 and IκBα.

Keywords

triptolide / human multiple myeloma / apoptosis / NF-κB/p65 / IκBα

Cite this article

Download citation ▾
Rong Zeng, Linlan Zeng, Yan Chen, Fei Zhao, Rui Li, Lu Wen, Chun Zhang. Triptolide-induced apoptosis by inactivating nuclear factor-kappa B apoptotic pathway in multiple myeloma in vitro. Current Medical Science, 2011, 31(4): 446-451 DOI:10.1007/s11596-011-0471-7

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

LiangM., FuJ.. Triptolide inhibits interferon-gamma-induced programmed death-1-ligand 1 surface expression in breast cancer cells. Cancer Lett, 2008, 270(2): 337-341

[2]

ShiX., JinY., ChengC., et al.. Triptolide inhibits Bcr-Abl transcription and induces apoptosis in STI571-resistant chronic myelogenous leukemia cells harboring T315I mutation. Clin Cancer Res, 2009, 15(5): 1686-1697

[3]

ZhouG.X., DingX.L., HuangJ.F., et al.. Apoptosis of human pancreatic cancer cells induced by tiptolide. World J Gestroenterol, 2008, 14(10): 1504-1509

[4]

ChangH.J., KimM.H., BaekM.K., et al.. Triptolide inhibits tumor promoter-induced uPAR expression via blocking NF-kappaB signaling in human gastric AGS cells. Anticancer Res, 2007, 27(5A): 3411-3417

[5]

ZhuW., OuY., LiY., et al.. A small-molecule triptolide suppresses angiogenesis and invasion of human anaplastic thyroid carcinoma cells via down-regulation of the nuclear factor-kappa B pathway. Mol Pharmacol, 2009, 75(4): 812-819

[6]

Sánchez-DuffhuesG., CalzadoM.A., de VinuesaA.G., et al.. Denbinobin inhibits nuclear factor-κB and induces apoptosis via reactive oxygen species generation in human leukemic cells. Biochem Pharmacol, 2009, 77(8): 1401-1409

[7]

GilmoreT.D.. Introduction to NF-κB: players, pathways, perspectives. Oncogene, 2006, 25(51): 6680-6684

[8]

WangB., KhachigianL.M., EsauL., et al.. A key role for early growth response-1 and nuclear factor-κB in mediating and maintaining GRO/CXCR2 proliferative signaling in esophageal cancer. Mol Cancer Res, 2009, 7(5): 755-764

[9]

TangX.Y., ZhuY.Q., TaoW.H., et al.. Synergistic effect of triptolide combined with 5-fluorouracil on colon carcinoma. Postgrad Med J, 2007, 83(979): 338-343

[10]

ClarkeR., ShajahanA.N., RigginsR.B., et al.. Gene network signaling in hormone responsiveness modifies apoptosis and autophagy in breast cancer cells. J Steroid Biochem Mol Biol, 2009, 114(1–2): 8-20

[11]

KarinM., LinA.. NF-kappaB at the crossroads of life and death. Nat Immunol, 2002, 3(3): 221-227

[12]

CarterB.Z., MakD.H., SchoberW.D., et al.. Triptolide induces caspase-dependent cell death mediated via the mitochondrial pathway. Blood, 2006, 108(2): 630-637

[13]

LiangJ., LuoG., NingX., et al.. Differential expression of calcium-related genes in gastric cancer cells transfected with cellular prion protein. Biochem Cell Biol, 2007, 85(3): 375-383

[14]

TschaharqanehD., EhemannV., NussbaumT., et al.. Non-specific effects of siRNAs on tumor cells with implications on therapeutic applicability using RNA interference. Pathol Oncol Res, 2007, 13(2): 84-90

[15]

MaddikaS., MendozaF.J., HauffK., et al.. Cancer-selective therapy of the future: apoptin and its mechanism of action. Cancer Biol Ther, 2006, 5(1): 10-19

[16]

PrasadR.C., WangX.L., LawB.K., et al.. Identification of genes, including the gene encoding P27kip1, regulated by serine 276 phosphorylation of the p65 subunit of NF-κB. Cancer Lett, 2009, 275(1): 139-149

[17]

BredelM., ScholtensD.M., HarshG.R., et al.. A network model of a cooperative genetic landscape in brain tumors. JAMA, 2009, 302(3): 261-275

[18]

BiswasD.K., ShiQ., BailyS., et al.. NF-κB activation in human breast cancer specimens and its role in cell proliferation and apoptosis. Proc Natl Acad Sci USA, 2004, 101(27): 10 137-10 142

[19]

Grosjean-RaillardJ., TaillerM., AdèsL., et al.. ATM mediates constitutive NF-κB activation in high risk myelodysplastic syndrome and acute myeloid leukemia. Oncogene, 2009, 28(8): 1099-1109

[20]

YunJ.M., AfaqF., KhanN., et al.. Delphinidin, an anthocyanidin in pigmented fruits and vegetables, induces apoptosis and cell cycle arrest in human colon cancer HCT116 cells. Mol Carcinoq, 2009, 48(3): 260-270

[21]

SuC.C., ChenG.W., LinJ.G., et al.. Curcumin inhibits cell migration of human colon cancer Colo 205 cells through the inhibition of nuclear factor κB/p65 and down-regulates cyclooxygenase-2 and matrix metalloproteinase-2 expression. Anticancer Res, 2006, 26(2A): 1281-1288

[22]

ShishodiaS., AminH.M., LaiR., et al.. Curcumin (diferuloylmethane) inhibits constitutive NF-κB activation, induces G1/S arrest, suppresses proliferation, and induces apoptosis in mantle cell lymphoma. Bio Pharm, 2005, 70(5): 700-713

[23]

TanakaH., HoshikawaY., Oh-haraT., et al.. PRMT5, a novel TRAIL receptor-binding protein, inhibits TRAIL-induced apoptosis via nuclear factor-kappaB activation. Mol Cancer Res, 2009, 7(4): 557-569

[24]

SakamotoK., MaedaS., HikibaY., et al.. Constitutive NF-kappaB activation in colorectal carcinoma plays a key role in angiogenesis, promoting tumor growth. Clin Cancer Res, 2009, 15(7): 2248-2258

[25]

BenitezD.A., HermosoM.A., Pozo-GuisadoE., et al.. Regulation of cell survival by resveratrol involves inhibition of NF kappaB-regulated gene expression in prostate cancer cells. Prostate, 2009, 69(10): 1045-1054

[26]

BatsiC., MarkopoulouS., KontargirisE., et al.. Bcl-2 blocks 2-methoxyestradiol induced leukemia cell apoptosis by a p27Kip1-dependent G1/S cell cycle arrest in conjunction with NF-kB activation. Biochem Pharmacol, 2009, 78(1): 33-44

AI Summary AI Mindmap
PDF

103

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/