Summary
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.
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Liang M, Fu J. Triptolide inhibits interferon-gamma-induced programmed death-1-ligand 1 surface expression in breast cancer cells. Cancer Lett, 2008,270(2):337–341
Shi X, Jin Y, Cheng C, 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
Zhou GX, Ding XL, Huang JF, et al. Apoptosis of human pancreatic cancer cells induced by tiptolide. World J Gestroenterol, 2008,14(10):1504–1509
Chang HJ, Kim MH, Baek MK, 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
Zhu W, Ou Y, Li Y, 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
Sánchez-Duffhues G, Calzado MA, de Vinuesa AG, 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
Gilmore TD. Introduction to NF-κB: players, pathways, perspectives. Oncogene, 2006,25(51):6680–6684
Wang B, Khachigian LM, Esau L, 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
Tang XY, Zhu YQ, Tao WH, et al. Synergistic effect of triptolide combined with 5-fluorouracil on colon carcinoma. Postgrad Med J, 2007,83(979):338–343
Clarke R, Shajahan AN, Riggins RB, 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
Karin M, Lin A. NF-kappaB at the crossroads of life and death. Nat Immunol, 2002,3(3):221–227
Carter BZ, Mak DH, Schober WD, et al. Triptolide induces caspase-dependent cell death mediated via the mitochondrial pathway. Blood, 2006,108(2):630–637
Liang J, Luo G, Ning X, 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
Tschaharqaneh D, Ehemann V, Nussbaum T, 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
Maddika S, Mendoza, FJ, Hauff K, et al. Cancer-selective therapy of the future: apoptin and its mechanism of action. Cancer Biol Ther, 2006,5(1):10–19
Prasad RC, Wang XL, Law BK, 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
Bredel M, Scholtens DM, Harsh GR, et al. A network model of a cooperative genetic landscape in brain tumors. JAMA, 2009,302(3):261–275
Biswas DK, Shi Q, Baily S, 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
Grosjean-Raillard J, Tailler M, Adès L, et al. ATM mediates constitutive NF-κB activation in high risk myelodysplastic syndrome and acute myeloid leukemia. Oncogene, 2009,28(8):1099–1109
Yun JM, Afaq F, Khan N, 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
Su CC, Chen GW, Lin JG, 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
Shishodia S, Amin HM, Lai R, 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
Tanaka H, Hoshikawa Y, Oh-hara T, 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
Sakamoto K, Maeda S, Hikiba Y, 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
Benitez DA, Hermoso MA, Pozo-Guisado E, 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
Batsi C, Markopoulou S, Kontargiris E, 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
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This project was supported by a grant from National Natural Sciences Foundation of China (No. 30700882).
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Zeng, R., Zeng, L., Chen, Y. et al. Triptolide-induced apoptosis by inactivating nuclear factor-kappa B apoptotic pathway in multiple myeloma in vitro . J. Huazhong Univ. Sci. Technol. [Med. Sci.] 31, 446–451 (2011). https://doi.org/10.1007/s11596-011-0471-7
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DOI: https://doi.org/10.1007/s11596-011-0471-7