β-elemene inhibits the proliferation of T24 bladder carcinoma cells through upregulation of the expression of Smad4

Lu,Xinsheng; Wang,Yi; Luo,Hongmei; Qiu,Weibin; Han,Hu; Chen,Xian; Yang,Luoyan

doi:10.3892/mmr.2012.1206

β-elemene inhibits the proliferation of T24 bladder carcinoma cells through upregulation of the expression of Smad4

Authors:
- Xinsheng Lu
- Yi Wang
- Hongmei Luo
- Weibin Qiu
- Hu Han
- Xian Chen
- Luoyan Yang
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Affiliations: Department of Urology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China, Department of Urology, Second Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China, Department of Histology and Embryology, University of South China, Hengyang, Hunan 421001, P.R. China
Published online on: November 28, 2012 https://doi.org/10.3892/mmr.2012.1206
Pages: 513-518

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Abstract

β-elemene, a non-cytotoxic antitumor reagent, inhibits the growth, proliferation and DNA synthesis of multiple types of malignant cells, resulting in the apoptosis or suppressed vascularization of tumors. β-elemene is also able to enhance the immunogenicity of the tumor cells and ameliorate systematic cellular immunity in the tumor‑bearing body. Moreover, β-elemene has the advantages of high efficiency, safety and low possibility of drug tolerance over other antitumor agents used in antitumor treatment. Therefore, β-elemene has great potential in clinical applications. However, the mechanism of β-elemene antitumor activity is largely unknown. The aim of this study was to investigate whether β-elemene is able to repress the proliferation of T24 bladder carcinoma cells through regulation of the expression of the tumor suppressor gene, Smad4. Results of a methylthiazolyl tetrazolium (MTT) assay indicated that the proliferation of T24 cells was repressed by β-elemene in a time- and concentration‑dependent manner. The lowest concentration of β-elemene to inhibit cell survival by >50% was determined using IC50 software. Microscopic observation also demonstrated the potential of β-elemene to induce the apoptosis of cancer cells. Western blot and RT-PCR analyses revealed that the expression of the Smad4 protein and mRNA was upregulated by treatment with β-elemene. Our results revealed that β-elemene was able to upregulate the expression of Smad4 in tumor cells to inhibit the proliferation of these cells.

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1	Xie T, Hua BJ and Sun M: Clinical progression in β-elemene research. Chin J Clin Oncol. 36:222009.(In Chinese).
2	Adio AM: (-)-trans-β-Elemene and related compounds: occurrence, synthesis, and anticancer activity. Tetrahedron. 65:5145–5159. 2009.
3	Damstrup L, Rygaard K, Spang-Thomsen M and Skovgaard Poulsen H: Expression of transforming growth factor beta (TGF beta) receptors and expression of TGF beta 1, TGF beta 2 and TGF beta 3 in human small cell lung cancer cell lines. Br J Cancer. 67:1015–1102. 1993. View Article : Google Scholar : PubMed/NCBI
4	Gordon KJ and Blobe GC: Role of transforming growth factor-beta superfamily signaling pathways in human disease. Biochim Biophys Acta. 1782:197–228. 2008. View Article : Google Scholar : PubMed/NCBI
5	Kamiya Y, Miyazono K and Miyazawa K: Smad7 inhibits transforming growth factor-beta family type I receptors through two distinct modes of interaction. J Biol Chem. 285:30804–30813. 2010. View Article : Google Scholar : PubMed/NCBI
6	Yang X and Zhang YG: Research progress in relationship between Smads and organ fibrosis. Medical Recapitulate. 17:112011.(In Chinese).
7	Li ZZ and Li Q: TGF-β/Smads signal pathway and its role in tumor. Medical Recapitulate. 17:62011.(In Chinese).
8	Lagna G, Hata A, Hemmati-Brivanlou A, et al: Partnership between DPC4 and SMAD proteins in TGF-beta signalling pathways. Nature. 383:832–836. 1996. View Article : Google Scholar : PubMed/NCBI
9	Cao B, Jiang MC, Lei ZY, et al: Effects of PLAB on apoptosis and Smad signal pathway of hypertrophic scar fibroblasts. J Asian Nat Prod Res. 10:147–157. 2008. View Article : Google Scholar : PubMed/NCBI
10	Li GQ, Xie BB, Chen YH, Li XL and Zou LJ: A research on adiotherapy sensitization by β-elemene on human adenocarcinoma implanted in naked mice and its correlation with HIF-1α CAIX. Chin J Clin Oncol. 38:62011.(In Chinese).
11	Liu J, Lo ZH, Liu YP, Qu XJ, Hou KZ, Xu L and Zhang Y: Influence of β-elemene on apoptosis of gastric cancer MGC803 cells and the mechanism. Shandong Medical Journal. 37:72010.(In Chinese).
12	Gao C and Wu R: A meta-analysis on β-elemene in single dosage or combination with chemotherapy/radiotherapy to treat brain malignancies. Chin J Clin Oncol. 37:72010.(In Chinese).
13	Li GQ, Xie BB, Chen YH, Li XL and Zou LJ: A research on correlation between radiotherapy sensitized by β-elemene and tumor vascularization. The Practical Journal of Cancer. 26:12011.(In Chinese).
14	Li LJ, Zou LJ, Zhang Z and Wang Q: The effect of β-elemene combined with radiation on DNA damage and repair in A549 cells. Chinese Journal of Radiation Oncology. 20:355–357. 2011.(In Chinese).
15	Li GQ, Li XL, Xie BB, Chen YH, Lei HW and Zou LJ: Study on the radiosensitivity of nude mice model transplanted lung adenocarcinoma cell treated by β-elemene. Chinese Journal of Radiological Medicine and Protection. 30:687–691. 2010.(In Chinese).
16	Li QQ, Wang G, Huang F, Banda M and Reed E: Antineoplastic effect of beta-elemene on prostate cancer cells and other types of solid tumour cells. J Pharm Pharmacol. 62:1018–1027. 2010. View Article : Google Scholar : PubMed/NCBI
17	Zhan YH, Liu ZY, Liu J, Liu YP, Qu XJ, Hou KZ and Wu B: An exploration on β-elemene influence of on kidney cancer 786–0 cells and its mechanism. Shandong Medical Journal. 51:302011.(In Chinese).
18	Samanta D and Datta PK: Alterations in the Smad pathway in human cancers. Front Biosci. 17:1281–1293. 2012. View Article : Google Scholar : PubMed/NCBI
19	Lampropoulos P, Zizi-Sermpetzoglou A, Rizos S, et al: TGF-beta signalling in colon carcinogenesis. Cancer Lett. 314:1–7. 2012. View Article : Google Scholar
20	Kretschmer C, Conradi A, Kemmner W and SternerKock A: Latent transforming growth factor binding protein 4 (LTBP4) is down regulated in mouse and human DCIS and mammary carcinomas. Cell Oncol (Dordrecht). 34:419–434. 2011. View Article : Google Scholar : PubMed/NCBI
21	Zhu T, Xu Y, Dong B, Zhang J, Wei Z, Xu Y and Yao Y: β-elemene inhibits proliferation of human glioblastoma cells through the activation of glia maturation factor β and induces sensitization to cisplatin. Oncol Rep. 26:405–413. 2011.
22	Chen WX, Lu Y, Wu JM, Gao M, Wang AY and Xu B: Beta-elemene inhibits melanoma growth and metastasis via suppressing vascular endothelial growth factor-mediated angiogenesis. Cancer Chemother Pharmacol. 67:799–808. 2011. View Article : Google Scholar : PubMed/NCBI
23	Zhu TZ, Zhao YS, Zhang JN, Li LJ, Zou LJ, Yao YQ and Xu YH: β-Elemene inhibits proliferation of human glioblastoma cells and causes cell-cycle G0/G1 arrest via mutually compensatory activation of MKK3 and MKK6. Int J Oncol. 38:419–426. 2011.
24	Li QQ, Wang G, Zhang M, Cuff CF, Huang L and Reed E: beta-Elemene, a novel plant-derived antineoplastic agent, increases cisplatin chemosensitivity of lung tumor cells by triggering apoptosis. Oncol Rep. 22:161–170. 2009.PubMed/NCBI
25	Liu J, Hu XJ, Jin B, Qu XJ, Hou KZ and Liu YP: β-Elemene induces apoptosis as well as protective autophagy in human non-small-cell lung cancer A549 cells. J Pharm Pharmacol. 64:146–153. 2012.
26	Li L, Xu L, Qu XJ, et al: Cbl-regulated Akt and ERK signals are involved in β-elemene-induced cell apoptosis in lung cancer cells. Mol Med Rep. 4:1243–1246. 2011.PubMed/NCBI
27	Ying J, Yang W, Xie CY, et al: Induction of caspase-3-dependent apoptosis in human leukemia HL-60 cells by δ-elemene. Yakugaku Zasshi. 131:1383–1394. 2011.