Triptolide potentiates lung cancer cells to cisplatin-induced apoptosis by selectively inhibiting the NER activity
Tóm tắt
Cisplatin and many other platinum-based compounds are important anticancer drugs that are used in treating many cancer types. The development of cisplatin-resistant cancer cells, however, quickly diminishes the effectiveness of these drugs and causes treatment failure. New strategies that reverse cancer cell drug resistance phenotype or sensitize cancer cells to these drugs, therefore, need to be explored in order to improve platinum drug-based cancer treatment. Triptolide is a bioactive ingredient isolated from Tripterygium wilfordii, a Chinese herbal medicine. Triptolide binds to the TFIIH basal transcription factor and is required for both transcription and nucleotide excision repair (NER), a DNA repair pathway involved in repairing DNA damage generated by the platinum-based anticancer drugs. Caspase-3 activation and cell growth inhibition assays were used to determine the effect of triptolide on cisplatin-induced apoptosis and cell growth in lung cancer cells. Real time PCR, immunoblotting, and expression of reef coral red protein were used to determine a mechanism through which the presence of triptolide increased cisplatin-induced apoptosis of the lung cancer cells. Our caspase-3 activation studies demonstrated that the presence of low-levels of triptolide greatly increased the cisplatin-induced apoptosis of HTB182, A549, CRL5810, and CRL5922 lung cancer cells. The results of our cell growth inhibition studies revealed that the presence of low-levels triptolide itself had little effect on cell growth but greatly enhanced cisplatin-induced cell growth inhibition in both A549 and HTB182 cells. The results of our reef coral-red protein reporter expression studies indicated that the presence of low-levels triptolide did not affect expression of the reef coral-red protein from pDsRed2-C1 plasmid but greatly inhibited expression of the reef coral-red protein from cisplatin-damaged pDsRed2-C1 plasmid DNA in A549 cells. In addition, the results of our protein phosphorylation studies indicated that the presence of low-levels triptolide caused a decrease for cisplatin-induced CHK1 phosphorylation at Ser317/345 but an increase for cisplatin-induced ATM phosphorylation at Ser1981 in both HTB182 and A549 cells. The results of our studies suggest that the presence of low-levels of triptolide potentiates lung cancer cells to cisplatin treatment by selectively inhibiting NER activity, resulting in an increase in apoptosis of the lung cancer cells.
Tài liệu tham khảo
Perry M. The chemotherapy source book. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2001.
Kufe DW, Bast RC, Hait WN, Hong WK, Pollock RE, Weichselbaum RR, et al. Cancer medicine. 7th ed. London: BC Decker; 2006.
Friedberg EC, Walker GC, Siede W, Wood RD, Schultz RA, Ellenberger T. DNA repair and Mutagenesis. 2nd ed. Washington, D.C.: ASM Press; 2006.
Chen Z, Xu XS, Yang J, Wang G. Defining the function of XPC protein in psoralen and cisplatin-mediated DNA repair and mutagenesis. Carcinogenesis. 2003;24:1111–21.
Wang G, Chuang L, Zhang X, Colton S, Dombkowski A, Reiners J, et al. The initiative role of XPC protein in cisplatin DNA damaging treatment-mediated cell cycle regulation. Nucleic Acids Res. 2004;32:2231–40.
Colton SL, Xu XS, Wang YA, Wang G. The involvement of ataxia-telangiectasia mutated protein activation in nucleotide excision repair-facilitated cell survival with cisplatin treatment. J Biol Chem. 2006;281:27117–25.
Kupchan SM, Court WA, Dailey Jr RG, Gilmore CJ, Bryan RF. Triptolide and tripdiolide, novel antileukemic diterpenoid triepoxides from Tripterygium wilfordii. J Am Chem Soc. 1972;94:7194–5.
Lu H, Hachida M, Enosawa S, Li XK, Suzuki S, Koyanagi H. Immunosuppressive effect of triptolide in vitro. Transplant Proc. 1999;31:2056–7.
Qiu D, Kao PN. Immunosuppressive and anti-inflammatory mechanisms of triptolide, the principal active diterpenoid from the Chinese medicinal herb Tripterygium wilfordii Hook. f. Drugs R D. 2003;4:1–18.
Titov D, Gilman B, He Q, Bhat S, Low W-K, Dang Y, et al. XPB, a subunit of TFIIH, is a target of the natural product triptolide. Nature Chem Biol. 2011;7:182–8.
Manzo S, Zhou ZL, Wang YQ, Marinello J, He JX, Li YC, et al. Natural product triptolide mediates cancer cell death by triggering CDK7-dependent degradation of RNA polymerase II. Cancer Res. 2012;72:5363–73.
Mujumdar N, Mackenzie TN, Dudeja V, Chugh R, Antonoff MB, Borja-Cacho D, et al. Triptolide induces cell death in pancreatic cancer cells by apoptotic and autophagic pathways. Gastroenterology. 2010;39:598–608.
Banerjee S, Sangwan V, McGinn O, Chugh R, Dudeja V, Vickers SM, et al. Triptolide-induced cell death in pancreatic cancer is mediated by O-GlcNAc modification of transcription factor Sp1. J Biol Chem. 2013;288:33927–38.
Wang Y, Lu JJ, He L, Yu Q. Triptolide (TPL) inhibits global transcription by inducing proteasome-dependent degradation of RNA polymerase II (Pol II). PLoS One. 2011;6, e23993.
Chang WT, Kang JJ, Lee KY, Wei K, Anderson E, Gotmare S, et al. Triptolide and chemotherapy cooperate in tumor cell apoptosis. A role for the p53 pathway. J Biol Chem. 2001;276:2221–7.
Qiu D, Zhao G, Aoki Y, Shi L, Uyei A, Nazarian S, et al. Immunosuppressant PG490 (triptolide) inhibits T-cell interleukin-2 expression at the level of purine-box/nuclear factor of activated T-cells and NF-kappaB transcriptional activation. J Biol Chem. 1999;274:13443–50.
Westerheide SD, Kawahara TL, Orton K, Morimoto RI. Triptolide, an inhibitor of the human heat shock response that enhances stress-induced cell death. J Biol Chem. 2006;281:9616–22.
Sancar A, Lindsey-Boltz LA, Unsal-Kaçmaz K, Linn S. Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu Rev Biochem. 2004;73:39–85.
Dai Y, Grant S. New insights into checkpoint kinase 1 in the DNA damage response signaling network. Clin Cancer Res. 2010;16:376–83.
Chen Y, Poon RY. The multiple checkpoint functions of CHK1 and CHK2 in maintenance of genome stability. Front Biosci. 2008;13:5016–29.
Thompson R, Eastman A. The cancer therapeutic potential of Chk1 inhibitors: how mechanistic studies impact on clinical trial design. Br J Clin Pharmacol. 2013;76:358–69.
Brown EJ, Baltimore D. ATR disruption leads to chromosomal fragmentation and early embryonic lethality. Genes Dev. 2000;14:397–402.
Bakkenist CJ, Kastan MB. DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature. 2003;421:499–506.
Wang P, Qiu W, Dudgeon C, Liu H, Huang C, Zambetti GP, et al. PUMA is directly activated by NF-κB and contributes to TNF-α-induced apoptosis. Cell Death Differ. 2009;16:1192–202.
Wu ZH, Miyamoto S. Induction of a pro-apoptotic ATM-NF-kappaB pathway and its repression by ATR in response to replication stress. EMBO J. 2008;27:1963–73.
Zhovmer A, Oksenych V, Coin F. Two sides of the same coin: TFIIH complexes in transcription and DNA repair. The Scientific World J. 2010;10:633–43.
Compe E, Egly JM. TFIIH: when transcription met DNA repair. Nat Rev Mol Cell Biol. 2013;13:343–54.
Whitesell L, Mimnaugh EG, De Costa B, Myers CE, Neckers LM. Inhibition of heat shock protein HSP90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins: essential role for stress proteins in oncogenic transformation. Proc Natl Acad Sci USA. 1994;91:8324–8.
Ho JN, Byun SS, Lee S, Oh JJ, Hong SK, Lee SE, et al. Synergistic antitumor effect of triptolide and Cisplatin in Cisplatin resistant human bladder cancer cells. J Urol. 2015;193:1016–22.
Li Y, Hu S. Triptolide sensitizes liver cancer cell lines to chemotherapy in vitro and in vivo. Panminerva Med. 2014;56:211–20.
Zhong YY, Chen HP, Tan BZ, Yu HH, Huang XS. Triptolide avoids cisplatin resistance and induces apoptosis via the reactive oxygen species/nuclear factor-κB pathway in SKOV3 < sup > PT</sup > platinum-resistant human ovarian cancer cells. Oncol Lett. 2013;6:1084–92.
Zhu W, Li J, Wu S, Li S, Le L, Su X, et al. Triptolide cooperates with Cisplatin to induce apoptosis in gemcitabine-resistant pancreatic cancer. Pancreas. 2012;41:1029–38.
Li CJ, Chu CY, Huang LH, Wang MH, Sheu LF, Yeh JI, et al. Synergistic anticancer activity of triptolide combined with cisplatin enhances apoptosis in gastric cancer in vitro and in vivo. Cancer Lett. 2012;319:203–13.
Matsui Y, Watanabe J, Ikegawa M, Kamoto T, Ogawa O, Nishiyama H. Cancer-specific enhancement of cisplatin-induced cytotoxicity with triptolide through an interaction of inactivated glycogen synthase kinase-3beta with p53. Oncogene. 2008;27:4603–14.
Lomonaco SL, Xu XS, Wang G. The role of Bcl-x(L) protein in nucleotide excision repair-facilitated cell protection against cisplatin-induced apoptosis. DNA Cell Biol. 2009;28:285–94.