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Article

β-elemonic acid inhibits the cell proliferation of human lung adenocarcinoma A549 cells: The role of MAPK, ROS activation and glutathione depletion

  • Authors:
    • Tsu‑Tuan Wu
    • Chien‑Lin Lu
    • Hen‑I Lin
    • Bing‑Fang Chen
    • Guey‑Mei Jow
  • View Affiliations / Copyright

    Affiliations: Department of Respiratory Therapy, Fu Jen Catholic University, New Taipei City, Taiwan, R.O.C., Division of Nephrology, Department of Medicine, Shin‑Kong Wu Ho‑Su Memorial Hospital, Taipei, Taiwan, R.O.C., School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan, R.O.C.
  • Pages: 227-234
    |
    Published online on: October 30, 2015
       https://doi.org/10.3892/or.2015.4368
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Abstract

β-elemonic acid, a known triterpene, exhibits anti-inflammatory effects, yet research on the pharmacological effects of β-elemonic acid is rare. We investigated the anticancer effects and the related molecular mechanisms of β‑elemonic acid on human non‑small cell lung cancer (NSCLC) A549 cells. The effects of β‑elemonic acid on the growth of A549 cells were studied using a 3‑(4,5)‑2,5‑diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected using Annexin V staining. The effect of β‑elemonic acid on the cell cycle of A549 cells was assessed using the propidium iodide method. The change in reactive oxygen species (ROS) was detected using a dichlorodihydrofluorescein diacetate (DCFH‑DA) assay with microscopic examination. The expression levels of Bcl‑2 family proteins, mitogen‑activated protein kinase (MAPK) family proteins and cyclooxygenase 2 (COX‑2) were detected using western blot analysis. Our data revealed that β‑elemonic acid strongly induced human A549 lung cancer cell death in a dose‑ and time‑dependent manner as determined by the MTT assay. β‑elemonic acid‑induced cell death was considered to be apoptotic when the phosphatidylserine exposure was observed using Annexin V staining. The death of human A549 lung cancer cells was caused by apoptosis induced by activation of ROS activity, increase in the sub‑G1 proportion, downregulation of Bcl‑2 expression, upregulation of Bax expression and inhibition of the MAPK signaling pathways. These results clearly demonstrated that β‑elemonic acid inhibits proliferation by inducing hypoploid cells and cell apoptosis. Moreover, the anticancer effects of β‑elemonic acid were related to the MAPK signaling pathway, ROS activation and glutathione depletion in human A549 lung cancer cells.
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1 

Anonymous. Analysis in cancer incidence and mortality - Taiwan. Epidermal Bull. 381–391. 1999.In Chinese.

2 

Sandler AB, Nemunaitis J, Denham C, von Pawel J, Cormier Y, Gatzemeier U, Mattson K, Manegold C, Palmer MC, Gregor A, et al: Phase III trial of gemcitabine plus cisplatin versus cisplatin alone in patients with locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 18:122–130. 2000.PubMed/NCBI

3 

Bonomi P, Kim K, Fairclough D, Cella D, Kugler J, Rowinsky E, Jiroutek M and Johnson D: Comparison of survival and quality of life in advanced non-small-cell lung cancer patients treated with two dose levels of paclitaxel combined with cisplatin versus etoposide with cisplatin: Results of an Eastern Cooperative Oncology Group trial. J Clin Oncol. 18:623–631. 2000.PubMed/NCBI

4 

Fisher DE: Apoptosis in cancer therapy: Crossing the threshold. Cell. 78:539–542. 1994. View Article : Google Scholar : PubMed/NCBI

5 

Kaufmann SH and Earnshaw WC: Induction of apoptosis by cancer chemotherapy. Exp Cell Res. 256:42–49. 2000. View Article : Google Scholar : PubMed/NCBI

6 

Medema JP, Scaffidi C, Kischkel FC, Shevchenko A, Mann M, Krammer PH and Peter ME: FLICE is activated by association with the CD95 death-inducing signaling complex (DISC). EMBO J. 16:2794–2804. 1997. View Article : Google Scholar : PubMed/NCBI

7 

Adams JM and Cory S: The Bcl-2 protein family: Arbiters of cell survival. Science. 281:1322–1326. 1998. View Article : Google Scholar : PubMed/NCBI

8 

Antonsson B and Martinou JC: The Bcl-2 protein family. Exp Cell Res. 256:50–57. 2000. View Article : Google Scholar : PubMed/NCBI

9 

Kausch I and Böhle A: Antisense oligonucleotide therapy in urology. J Urol. 168:239–247. 2002. View Article : Google Scholar : PubMed/NCBI

10 

McDonnell TJ, Beham A, Sarkiss M, Andersen MM and Lo P: Importance of the Bcl-2 family in cell death regulation. Experientia. 52:1008–1017. 1996. View Article : Google Scholar : PubMed/NCBI

11 

Farrow SN and Brown R: New members of the Bcl-2 family and their protein partners. Curr Opin Genet Dev. 6:45–49. 1996. View Article : Google Scholar : PubMed/NCBI

12 

Schmitt E, Sané AT, Steyaert A, Cimoli G and Bertrand R: The Bcl-xL and Bax-alpha control points: Modulation of apoptosis induced by cancer chemotherapy and relation to TPCK-sensitive protease and caspase activation. Biochem Cell Biol. 75:301–314. 1997.PubMed/NCBI

13 

Meade EA, McIntyre TM, Zimmerman GA and Prescott SM: Peroxisome proliferators enhance cyclooxygenase-2 expression in epithelial cells. J Biol Chem. 274:8328–8334. 1999. View Article : Google Scholar : PubMed/NCBI

14 

Pontsler AV, St Hilaire A, Marathe GK, Zimmerman GA and McIntyre TM: Cyclooxygenase-2 is induced in monocytes by peroxisome proliferator activated receptor gamma and oxidized alkyl phospholipids from oxidized low density lipoprotein. J Biol Chem. 277:13029–13036. 2002. View Article : Google Scholar : PubMed/NCBI

15 

Kalajdzic T, Faour WH, He QW, Fahmi H, Martel-Pelletier J, Pelletier JP and Di Battista JA: Nimesulide, a preferential cyclooxygenase 2 inhibitor, suppresses peroxisome prolif-erator-activated receptor induction of cyclooxygenase 2 gene expression in human synovial fibroblasts: Evidence for receptor antagonism. Arthritis Rheum. 46:494–506. 2002. View Article : Google Scholar : PubMed/NCBI

16 

Mitchell JA, Belvisi MG, Akarasereenont P, Robbins RA, Kwon OJ, Croxtall J, Barnes PJ and Vane JR: Induction of cyclo-oxygenase-2 by cytokines in human pulmonary epithelial cells: Regulation by dexamethasone. Br J Pharmacol. 113:1008–1014. 1994. View Article : Google Scholar : PubMed/NCBI

17 

Chen CC, Sun YT, Chen JJ and Chiu KT: TNF-alpha-induced cyclooxygenase-2 expression in human lung epithelial cells: Involvement of the phospholipase C-gamma 2, protein kinase C-alpha, tyrosine kinase, NF-kappa B-inducing kinase, and I-kappa B kinase 1/2 pathway. J Immunol. 165:2719–2728. 2000. View Article : Google Scholar : PubMed/NCBI

18 

Davis RJ: Signal transduction by the JNK group of MAP kinases. Cell. 103:239–252. 2000. View Article : Google Scholar : PubMed/NCBI

19 

Chang L and Karin M: Mammalian MAP kinase signalling cascades. Nature. 410:37–40. 2001. View Article : Google Scholar : PubMed/NCBI

20 

Kyriakis JM and Avruch J: Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev. 81:807–869. 2001.PubMed/NCBI

21 

Atta-ur-Rahman, Naz H, Fadimatou, Makhmoor T, Yasin A, Fatima N, Ngounou FN, Kimbu SF, Sondengam BL and Choudhary MI: Bioactive constituents from Boswellia papyrifera. J Nat Prod. 68:189–193. 2005. View Article : Google Scholar : PubMed/NCBI

22 

Lee HJ and Soliman MR: Anti-inflammatory steroids without pituitary-adrenal suppression. Science. 215:989–991. 1982. View Article : Google Scholar : PubMed/NCBI

23 

Mosmann T: Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J Immunol Methods. 65:55–63. 1983. View Article : Google Scholar : PubMed/NCBI

24 

Jow GM, Wu YC, Guh JH and Teng CM: Armepavine oxalate induces cell death on CCRF-CEM leukemia cell line through an apoptotic pathway. Life Sci. 75:549–557. 2004. View Article : Google Scholar : PubMed/NCBI

25 

An FF, Liu YC, Zhang WW and Liang L: Dihydroartemisinine enhances dictamnine-induced apoptosis via a caspase dependent pathway in human lung adenocarcinoma A549 cells. Asian Pac J Cancer Prev. 14:5895–5900. 2013. View Article : Google Scholar : PubMed/NCBI

26 

Koopman G, Reutelingsperger CP, Kuijten GA, Keehnen RM, Pals ST and van Oers MH: Annexin V for flow cytometric detection of phosphatidylserine expression on B cells undergoing apoptosis. Blood. 84:1415–1420. 1994.PubMed/NCBI

27 

Vaux DL and Korsmeyer SJ: Cell death in development. Cell. 96:245–254. 1999. View Article : Google Scholar : PubMed/NCBI

28 

Shamas-Din A, Kale J, Leber B and Andrews DW: Mechanisms of action of Bcl-2 family proteins. Cold Spring Harb Perspect Biol. 5:a0087142013. View Article : Google Scholar : PubMed/NCBI

29 

Wada T and Penninger JM: Mitogen-activated protein kinases in apoptosis regulation. Oncogene. 23:2838–2849. 2004. View Article : Google Scholar : PubMed/NCBI

30 

Pelicano H, Carney D and Huang P: ROS stress in cancer cells and therapeutic implications. Drug Resist Updat. 7:97–110. 2004. View Article : Google Scholar : PubMed/NCBI

31 

Põld M, Zhu LX, Sharma S, Burdick MD, Lin Y, Lee PP, Põld A, Luo J, Krysan K, Dohadwala M, et al: Cyclooxygenase-2-dependent expression of angiogenic CXC chemokines ENA-78/CXC Ligand (CXCL) 5 and interleukin-8/CXCL8 in human non-small cell lung cancer. Cancer Res. 64:1853–1860. 2004. View Article : Google Scholar : PubMed/NCBI

32 

Bakhle YS: COX-2 and cancer: A new approach to an old problem. Br J Pharmacol. 134:1137–1150. 2001. View Article : Google Scholar : PubMed/NCBI

33 

Newton R, Kuitert LM, Bergmann M, Adcock IM and Barnes PJ: Evidence for involvement of NF-kappaB in the transcriptional control of COX-2 gene expression by IL-1beta. Biochem Biophys Res Commun. 237:28–32. 1997. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Wu TT, Lu CL, Lin HI, Chen BF and Jow GM: β-elemonic acid inhibits the cell proliferation of human lung adenocarcinoma A549 cells: The role of MAPK, ROS activation and glutathione depletion. Oncol Rep 35: 227-234, 2016.
APA
Wu, T., Lu, C., Lin, H., Chen, B., & Jow, G. (2016). β-elemonic acid inhibits the cell proliferation of human lung adenocarcinoma A549 cells: The role of MAPK, ROS activation and glutathione depletion. Oncology Reports, 35, 227-234. https://doi.org/10.3892/or.2015.4368
MLA
Wu, T., Lu, C., Lin, H., Chen, B., Jow, G."β-elemonic acid inhibits the cell proliferation of human lung adenocarcinoma A549 cells: The role of MAPK, ROS activation and glutathione depletion". Oncology Reports 35.1 (2016): 227-234.
Chicago
Wu, T., Lu, C., Lin, H., Chen, B., Jow, G."β-elemonic acid inhibits the cell proliferation of human lung adenocarcinoma A549 cells: The role of MAPK, ROS activation and glutathione depletion". Oncology Reports 35, no. 1 (2016): 227-234. https://doi.org/10.3892/or.2015.4368
Copy and paste a formatted citation
x
Spandidos Publications style
Wu TT, Lu CL, Lin HI, Chen BF and Jow GM: β-elemonic acid inhibits the cell proliferation of human lung adenocarcinoma A549 cells: The role of MAPK, ROS activation and glutathione depletion. Oncol Rep 35: 227-234, 2016.
APA
Wu, T., Lu, C., Lin, H., Chen, B., & Jow, G. (2016). β-elemonic acid inhibits the cell proliferation of human lung adenocarcinoma A549 cells: The role of MAPK, ROS activation and glutathione depletion. Oncology Reports, 35, 227-234. https://doi.org/10.3892/or.2015.4368
MLA
Wu, T., Lu, C., Lin, H., Chen, B., Jow, G."β-elemonic acid inhibits the cell proliferation of human lung adenocarcinoma A549 cells: The role of MAPK, ROS activation and glutathione depletion". Oncology Reports 35.1 (2016): 227-234.
Chicago
Wu, T., Lu, C., Lin, H., Chen, B., Jow, G."β-elemonic acid inhibits the cell proliferation of human lung adenocarcinoma A549 cells: The role of MAPK, ROS activation and glutathione depletion". Oncology Reports 35, no. 1 (2016): 227-234. https://doi.org/10.3892/or.2015.4368
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