Triptolide suppresses the proliferation and induces the apoptosis of nasopharyngeal carcinoma cells via the PI3K/Akt pathway

Wang,Mi; Chen ,Bo; Chai,Liang

doi:10.3892/ol.2018.9726

Triptolide suppresses the proliferation and induces the apoptosis of nasopharyngeal carcinoma cells via the PI3K/Akt pathway

Authors:
- Mi Wang
- Bo Chen
- Liang Chai
View Affiliations

Affiliations: Department of Otolaryngology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
Published online on: November 19, 2018 https://doi.org/10.3892/ol.2018.9726
Pages: 1372-1378

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Nasopharyngeal carcinoma (NPC) is an endothelium‑associated malignancy that is heavily influenced by Epstein Barr virus infection. Triptolide, extracted from Tripterygium wilfordii, has been proven to possess anti‑inflammatory, immunosuppressive and anti‑cancerous activity. Although the effect of triptolide on numerous cancer cell types has been outlined, its effect in NPC remained unclear. The present study investigated the effects and underlying mechanisms of triptolide in C666‑1 and NP69 cells. It was revealed that triptolide significantly inhibited proliferation and induced apoptosis in C666‑1 cells. Increased levels of cleaved‑caspase‑3 and apoptosis regulator BAX, decreased expression of apoptosis regulator Bcl‑2, and reduced phosphorylation of RAC‑α serine/threonine‑protein kinase (Akt), were responsible for this induction of apoptosis. Notably, pretreating C666‑1 cells with the phosphatidylinositol 3‑kinase (PI3K)/Akt inhibitor LY294002 suggested that with increasing concentrations of LY294002, triptolide exhibited decreasing ability to suppress proliferation and induce apoptosis in these cells. In conclusion, the results demonstrated that triptolide suppressed the proliferation and induced the apoptosis of C666‑1 cells in a PI3K/Akt‑dependent manner and therefore, may serve as a promising therapeutic candidate for NPC.

View Figures

View References

1	Lo KW, Chung GT and To KF: Deciphering the molecular genetic basis of NPC through molecular, cytogenetic, and epigenetic approaches. Semin Cancer Biol. 22:79–86. 2012. View Article : Google Scholar : PubMed/NCBI
2	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
3	Maxwell JH, Kumar B, Feng FY, McHugh JB, Cordell KG, Eisbruch A, Worden FP, Wolf GT, Prince ME, Moyer JS, et al: HPV-positive/p16-positive/EBV-negative nasopharyngeal carcinoma in white North Americans. Head Neck. 32:562–567. 2010.PubMed/NCBI
4	Dawson CW, Port RJ and Young LS: The role of the EBV-encoded latent membrane proteins LMP1 and LMP2 in the pathogenesis of nasopharyngeal carcinoma (NPC). Semin Cancer Biol. 22:144–153. 2012. View Article : Google Scholar : PubMed/NCBI
5	Shah KM, Stewart SE, Wei W, Woodman CB, O'Neil JD, Dawson CW and Young LS: The EBV-encoded latent membrane proteins, LMP2A and LMP2B, limit the actions of interferon by targeting interferon receptors for degradation. Oncogene. 28:3903–3914. 2009. View Article : Google Scholar : PubMed/NCBI
6	Dawson CW, Rickinson AB and Young LS: Epstein-barr virus latent membrane protein inhibits human epithelial cell differentiation. Nature. 344:777–780. 1990. View Article : Google Scholar : PubMed/NCBI
7	Allen MD, Young LS and Dawson CW: The Epstein-barr virus-encoded LMP2A and LMP2B proteins promote epithelial cell spreading and motility. J Virol. 79:1789–1802. 2005. View Article : Google Scholar : PubMed/NCBI
8	Oda K, Okada J, Timmerman L, Rodriguez-Viciana P, Stokoe D, Shoji K, Taketani Y, Kuramoto H, Knight ZA, Shokat KM and McCormick F: PIK3CA cooperates with other phosphatidylinositol 3′-kinase pathway mutations to effect oncogenic transformation. Cancer Res. 68:8127–8136. 2008. View Article : Google Scholar : PubMed/NCBI
9	Corson TW and Crews CM: Molecular understanding and modern application of traditional medicines: Triumphs and trials. Cell. 130:769–774. 2007. View Article : Google Scholar : PubMed/NCBI
10	Ma J, Dey M, Yang H, Poulev A, Pouleva R, Dorn R, Lipsky PE, Kennelly EJ and Raskin I: Anti-inflammatory and immunosuppressive compounds from Tripterygium wilfordii. Phytochemistry. 68:1172–1178. 2007. View Article : Google Scholar : PubMed/NCBI
11	Yang SX, Gao HL, Xie SS, Zhang WR and Long ZZ: Immunosuppression of triptolide and its effect on skin allograft survival. Int J Immunopharmacol. 14:963–969. 1992. View Article : Google Scholar : PubMed/NCBI
12	Banerjee S, Sangwan V, McGinn O, Chugh R, Dudeja V, Vickers SM and Saluja AK: Triptolide-induced cell death in pancreatic cancer is mediated by O-GlcNAc modification of transcription factor Sp1. J Biol Chem. 288:33927–33938. 2013. View Article : Google Scholar : PubMed/NCBI
13	Wu PP, Liu KC, Huang WW, Ma CY, Lin H, Yang JS and Chung JG: Triptolide induces apoptosis in human adrenal cancer NCI-H295 cells through a mitochondrial-dependent pathway. Oncol Rep. 25:551–557. 2011.PubMed/NCBI
14	Yang S, Chen J, Guo Z, Xu XM, Wang L, Pei XF, Yang J, Underhill CB and Zhang L: Triptolide inhibits the growth and metastasis of solid tumors. Mol Cancer Ther. 2:65–72. 2003.PubMed/NCBI
15	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
16	Xiong J, Su T, Qu Z, Yang Q, Wang Y, Li J and Zhou S: Triptolide has anticancer and chemosensitization effects by down-regulating Akt activation through the MDM2/REST pathway in human breast cancer. Oncotarget. 7:23933–23946. 2016. View Article : Google Scholar : PubMed/NCBI
17	Chen Q, Lu Z, Jin Y, Wu Y and Pan J: Triptolide inhibits Jak2 transcription and induces apoptosis in human myeloproliferative disorder cells bearing Jak2V617F through caspase-3-mediated cleavage of Mcl-1. Cancer Lett. 291:246–255. 2010. View Article : Google Scholar : PubMed/NCBI
18	Carter BZ, Mak DH, Schober WD, Dietrich MF, Pinilla C, Vassilev LT, Reed JC and Andreeff M: Triptolide sensitizes AML cells to TRAIL-induced apoptosis via decrease of XIAP and p53-mediated increase of DR5. Blood. 111:3742–3750. 2008. View Article : Google Scholar : PubMed/NCBI
19	Liu L, Li G, Li Q, Jin Z, Zhang L, Zhou J, Hu X, Zhou T, Chen J and Gao N: Triptolide induces apoptosis in human leukemia cells through caspase-3-mediated ROCK1 activation and MLC phosphorylation. Cell Death Dis. 4:e9412013. View Article : Google Scholar : PubMed/NCBI
20	Wang PY, Zeng WJ, Liu J, Wu YL, Ma Y, Zeng Z, Pang JY, Zhang XK, Yan X, Wong AST and Zeng JZ: TRC4, an improved triptolide derivative, specifically targets to truncated form of retinoid X receptor-alpha in cancer cells. Biochemical pharmacology. 124:19–28. 2017. View Article : Google Scholar : PubMed/NCBI