Tetrandrine induces apoptosis and triggers a caspase cascade in U2-OS and MG-63 cells through the intrinsic and extrinsic pathways

Tao,Li-Jiang; Zhou,Xin-Die; Shen,Cheng-Chun; Liang,Cheng-Zhen; Liu,Bing; Tao,Yiqing; Tao,Hui-Min

doi:10.3892/mmr.2013.1761

Tetrandrine induces apoptosis and triggers a caspase cascade in U2-OS and MG-63 cells through the intrinsic and extrinsic pathways

Authors:
- Li-Jiang Tao
- Xin-Die Zhou
- Cheng-Chun Shen
- Cheng-Zhen Liang
- Bing Liu
- Yiqing Tao
- Hui-Min Tao
View Affiliations

Affiliations: Department of Orthopedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China
Published online on: October 29, 2013 https://doi.org/10.3892/mmr.2013.1761
Pages: 345-349

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

Although neoadjuvant chemotherapy has improved the survival rate of osteosarcoma patients, drug resistance remains a predominant obstacle to improving efficacy and necessitates the development of novel chemotherapeutical agents. The aim of this study was to investigate whether tetrandrine (TET) induces apoptosis in the U-2OS and MG-63 osteosarcoma cell lines and to further determine the underlying mechanism. This study investigated the effects of TET on osteosarcoma in vitro. To examine the antitumor effects of TET on osteosarcoma, the two osteosarcoma cell lines were treated with TET and subjected to apoptosis assays. The results revealed that TET induced the apoptosis of osteosarcoma cells in a time- and dose-dependent manner. Furthermore, the apoptosis of osteosarcoma cells was accompanied by increased cytochrome c (Cyto-C), apoptotic protease-activating factor (Apaf)-1, Bid and Bax activation and reduced Bcl-2 and Bcl-xl activation, demonstrating that the apoptosis may have occurred through the mitochondrial pathway. In conclusion, the results suggest that TET is a promising agent for osteosarcoma therapy.

View Figures

View References

1	Lin YT, Huang AC, Kuo CL, et al: Induction of cell cycle arrest and apoptosis in human osteosarcoma U-2 OS cells by Solanum lyratum extracts. Nutr Cancer. 65:469–479. 2013. View Article : Google Scholar : PubMed/NCBI
2	Liang CZ, Zhang X, Li H, et al: Gallic acid induces the apoptosis of human osteosarcoma cells in vitro and in vivo via the regulation of mitogen-activated protein kinase pathways. Cancer Biother Radiopharm. 27:701–710. 2012. View Article : Google Scholar : PubMed/NCBI
3	Cho HJ, Lee TS, Park JB, et al: Disulfiram suppresses invasive ability of osteosarcoma cells via the inhibition of MMP-2 and MMP-9 expression. J Biochem Mol Biol. 40:1069–1076. 2007. View Article : Google Scholar : PubMed/NCBI
4	Huang G, Mills L and Worth LL: Expression of human glutathione S-transferase P1 mediates the chemosensitivity of osteosarcoma cells. Mol Cancer Ther. 6:1610–1619. 2007. View Article : Google Scholar : PubMed/NCBI
5	Zhang B, Shi ZL, Liu B, Yan XB, Feng J and Tao HM: Enhanced anticancer effect of gemcitabine by genistein in osteosarcoma: the role of Akt and nuclear factor-κB. Anticancer Drugs. 21:288–296. 2010.PubMed/NCBI
6	Posthumadeboer J, van Egmond PW, Helder MN, et al: Targeting JNK-interacting-protein-1 (JIP1) sensitises osteosarcoma to doxorubicin. Oncotarget. 3:1169–1181. 2012.PubMed/NCBI
7	Zhang Y, Wei RX, Zhu XB, Cai L, Jin W and Hu H: Tanshinone IIA induces apoptosis and inhibits the proliferation, migration, and invasion of the osteosarcoma MG-63 cell line in vitro. Anticancer Drugs. 23:212–219. 2012. View Article : Google Scholar : PubMed/NCBI
8	Wu HY, Lin TK, Kuo HM, et al: Phyllanthus urinaria induces apoptosis in human osteosarcoma 143B cells via activation of Fas/FasL- and mitochondria-mediated pathways. Evid Based Complement Alternat Med. 2012:1–13. 2012.
9	Teh BS, Chen P, Lavin MF, Seow WK and Thong YH: Demonstration of the induction of apoptosis (programmed cell death) by tetrandrine, a novel anti-inflammatory agent. Int J Immunopharmacol. 13:1117–1126. 1991. View Article : Google Scholar : PubMed/NCBI
10	Lai YL, Chen YJ, Wu TY, et al: Induction of apoptosis in human leukemic U937 cells by tetrandrine. Anticancer Drugs. 9:77–81. 1998. View Article : Google Scholar : PubMed/NCBI
11	Dong Y, Yang MM and Kwan CY: In vitro inhibition of proliferation of HL-60 cells by tetrandrine and coriolus versicolor peptide derived from Chinese medicinal herbs. Life Sci. 60:PL135–140. 1997. View Article : Google Scholar : PubMed/NCBI
12	Cho HS, Chang SH, Chung YS, et al: Synergistic effect of ERK inhibition on tetrandrine-induced apoptosis in A549 human lung carcinoma cells. J Vet Sci. 10:23–28. 2009. View Article : Google Scholar : PubMed/NCBI
13	He BC, Gao JL, Zhang BQ, et al: Tetrandrine inhibits Wnt/β-catenin signaling and suppresses tumor growth of human colorectal cancer. Mol Pharmacol. 79:211–219. 2011.
14	Yoo SM, Oh SH, Lee SJ, et al: Inhibition of proliferation and induction of apoptosis by tetrandrine in HepG2 cells. J Ethnopharmacol. 81:225–229. 2002. View Article : Google Scholar : PubMed/NCBI
15	Wei J, Liu B, Wang L, Qian X, Ding Y and Yu L: Synergistic interaction between tetrandrine and chemotherapeutic agents and influence of tetrandrine on chemotherapeutic agent-associated genes in human gastric cancer cell lines. Cancer Chemother Pharmacol. 60:703–711. 2007. View Article : Google Scholar
16	Meng LH, Zhang H, Hayward L, Takemura H, Shao RG and Pommier Y: Tetrandrine induces early G1 arrest in human colon carcinoma cells by down-regulating the activity and inducing the degradation of G1-S-specific cyclin-dependent kinases and by inducing p53 and p21Cip1. Cancer Res. 64:9086–9092. 2004. View Article : Google Scholar : PubMed/NCBI
17	Zhang Y, Wang C, Wang H, Wang K, Du Y and Zhang J: Combination of tetrandrine with cisplatin enhances cytotoxicity through growth suppression and apoptosis in ovarian cancer in vitro and in vivo. Cancer Lett. 304:21–32. 2011. View Article : Google Scholar : PubMed/NCBI
18	Liu C, Gong K, Mao X and Li W: Tetrandrine induces apoptosis by activating reactive oxygen species and repressing Akt activity in human hepatocellular carcinoma. Int J Cancer. 129:1519–1531. 2011. View Article : Google Scholar : PubMed/NCBI
19	Li X, Su B, Liu R, Wu D and He D: Tetrandrine induces apoptosis and triggers caspase cascade in human bladder cancer cells. J Surg Res. 166:e45–51. 2011. View Article : Google Scholar : PubMed/NCBI
20	Lima RT, Busacca S, Almeida GM, Gaudino G, Fennell DA and Vasconcelos MH: MicroRNA regulation of core apoptosis pathways in cancer. Eur J Cancer. 47:163–174. 2011. View Article : Google Scholar : PubMed/NCBI
21	Fernandez-Luna JL: Regulation of pro-apoptotic BH3-only proteins and its contribution to cancer progression and chemoresistance. Cell Signal. 20:1921–1926. 2008. View Article : Google Scholar : PubMed/NCBI
22	Liang CZ, Zhang JK, Shi Z, Liu B, Shen CQ and Tao HM: Matrine induces caspase-dependent apoptosis in human osteosarcoma cells in vitro and in vivo through the upregulation of Bax and Fas/FasL and downregulation of Bcl-2. Cancer Chemother Pharmacol. 69:317–331. 2011. View Article : Google Scholar : PubMed/NCBI
23	Ito Y, Pandey P, Sporn MB, Datta R, Kharbanda S and Kufe D: The novel triterpenoid CDDO induces apoptosis and differentiation of human osteosarcoma cells by a caspase-8 dependent mechanism. Mol Pharmacol. 59:1094–1099. 2001.PubMed/NCBI
24	Oh SH and Lee BH: Induction of apoptosis in human hepatoblastoma cells by tetrandrine via caspase-dependent Bid cleavage and cytochrome c release. Biochem Pharmacol. 66:725–731. 2003. View Article : Google Scholar : PubMed/NCBI
25	Shukla RK, Kumar A, Gurbani D, Pandey AK, Singh S and Dhawan A: TiO₂ nanoparticles induce oxidative DNA damage and apoptosis in human liver cells. Nanotoxicology. 7:48–60. 2013.
26	Kaseta MK, Khaldi L, Gomatos IP, et al: Prognostic value of bax, bcl-2, and p53 staining in primary osteosarcoma. J Surg Oncol. 97:259–266. 2008. View Article : Google Scholar : PubMed/NCBI
27	Cao X, Bennett RL and May WS: c-Myc and caspase-2 are involved in activating Bax during cytotoxic drug-induced apoptosis. J Biol Chem. 283:14490–14496. 2008. View Article : Google Scholar : PubMed/NCBI
28	Schmitz I, Kirchhoff S and Krammer PH: Regulation of death receptor-mediated apoptosis pathways. Int J Biochem Cell Biol. 32:1123–1136. 2000. View Article : Google Scholar : PubMed/NCBI
29	Luo X, Budihardjo I, Zou H, Slaughter C and Wang X: Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell. 94:481–490. 1998. View Article : Google Scholar : PubMed/NCBI
30	Liu X, Kim CN, Yang J, Jemmerson R and Wang X: Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell. 86:147–157. 1996. View Article : Google Scholar : PubMed/NCBI
31	Wang K, Yin XM, Chao DT, Milliman CL and Korsmeyer SJ: BID: a novel BH3 domain-only death agonist. Genes Dev. 10:2859–2869. 1996. View Article : Google Scholar : PubMed/NCBI