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Anticancer effect of icaritin on human lung cancer cells through inducing s phase cell cycle arrest and apoptosis

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Summary

Icaritin, a prenylflavonoid derivative from Epimedium Genus, has been shown to exhibit many pharmacological and biological activities. However, the function and the underlying mechanisms of icaritin in human non-small cell lung cancer have not been fully elucidated. The purpose of this study was to investigate the anticancer effects of icaritin on A549 cells and explore the underlying molecular mechanism. The cell viability after icaritin treatment was tested by MTT assay. The cell cycle distribution, apoptosis and reactive oxygen species (ROS) levels were analyzed by flow cytometry. The mRNA and protein expression levels of the genes involved in proliferation and apoptosis were respectively detected by RT-PCR and Western blotting. The results demonstrated that icaritin induced cell cycle arrest at S phase, and down-regulated the expression levels of S regulatory proteins such as Cyclin A and CDK2. Icaritin also induced cell apoptosis characterized by positive Hoechst 33258 staining, accumulation of the Annexin V-positive cells, increased ROS level and alteration in Bcl-2 family proteins expression. Moreover, icaritin induced sustained phosphorylation of ERK and p38 MAPK. These findings suggested that icaritin might be a new potent inhibitor by inducing S phase arrest and apoptosis in human lung carcinoma A549 cells.

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References

  1. Jiang L, Luo M, Liu D, et al. BAD overexpression inhibits cell growth and induces apoptosis via mitochondrial-dependent pathway in non-small cell lung cancer. Cancer Cell Int, 2013,13(1):53

    Article  PubMed Central  PubMed  Google Scholar 

  2. Roomi MW, Kalinovsky T, Niedzwiecki A, et al. Modulation of u-PA, MMPs and their inhibitors by a novel nutrient mixture in human lung cancer and mesothelioma cell lines. Int J Oncol, 2013,42(6):1883–1889

    CAS  PubMed Central  PubMed  Google Scholar 

  3. Jemal A, Siegel R, Ward E, et al. Cancer statistics. CA Cancer J Clin, 2009,59(4):225–249

    Article  PubMed  Google Scholar 

  4. Zhu DY, Lou YJ. Inducible effects of icariin, icaritin, and desmethylicaritin on directional differentiation of embryonic stem cells into cardiomyocytes in vitro. Acta Pharmacol Sin, 2005,26(4):477–485

    Article  CAS  PubMed  Google Scholar 

  5. Zhang G., Qin L, Sheng H, et al. A novel semisynthesized small molecule icaritin reduces incidence of steroid-associated osteonecrosis with inhibition of both thrombosis and lipid-deposition in a dose-dependent manner. Bone, 2009,44(2):345–356

    Article  CAS  PubMed  Google Scholar 

  6. Wang Z, Zhang X, Wang H, et al. Neuroprotective effects of icaritin against beta amyloid-induced neurotoxicity in primary cultured rat neuronal cells via estrogen-dependent pathway. Neuroscience, 2007,145(3):911–922

    Article  CAS  PubMed  Google Scholar 

  7. Huang J, Yuan L, Wang X, et al. Icaritin and its glycosides enhance osteoblastic, but suppress osteoclastic, differentiation and activity in vitro. Life Sci, 2007,81(10):832–840

    Article  CAS  PubMed  Google Scholar 

  8. Li QH, Huai L, Zhang CP, et al. Icaritin induces AML cell apoptosis via the MAPK/ERK and PI3K/AKT signal pathways. Int J Hematol, 2013,97(5):617–623

    Article  CAS  PubMed  Google Scholar 

  9. Guo YM, Zhang XT, Meng J, et al. An anticancer agent icaritin induces sustained activation of the extracellular signal-regulated kinase (ERK) pathway and inhibits growth of breast cancer cells. Eur J Pharmacol, 2011,658(2–3):114–122

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Wang ZQ, Lou YJ. Proliferation-stimulating effects of icaritin and desmethylicaritin in MCF-7 cells. Eur J Pharmacol, 2004,504(3):147–153

    Article  CAS  PubMed  Google Scholar 

  11. Huang X, Zhu DY, Lou Y. A novel anticancer agent, icaritin, induced cell growth inhibition, G(1) arrest and mitochondrial transmembrane potential drop in human prostate carcinoma PC-3 cells. Eur J Pharmacol, 2007,564(1–3):26–36

    Article  CAS  PubMed  Google Scholar 

  12. Tong JS, Zhang QH, Huang X, et al. Icaritin causes sustained ERK1/2 activation and induces apoptosis in human endometrial cancer cells. PLoS One, 2011,6(3):e16781

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. He J, Wang Y, Duan F, et al. Icaritin induces apoptosis of HepG2 cells via the JNK1 signaling pathway independent of the estrogen receptor. Planta Med, 2010,76(16):1834–1839

    Article  CAS  PubMed  Google Scholar 

  14. Mirzayans R, Andrais B, Scott A, et al. New insights into p53 signaling and cancer cell response to DNA damage: implications for cancer therapy. J Biomed Biotechnol, 2012,2012:170325

    Article  PubMed Central  PubMed  Google Scholar 

  15. Vogelstein B, Lane D, Levine AJ. Surfing the p53 network. Nature, 2000,408(6810):307–310

    Article  CAS  PubMed  Google Scholar 

  16. Zhang Y, Xu XM, He P. Tubeimoside-1 inhibits proliferation and induces apoptosis by increasing the Bax to Bcl-2 ratio and decreasing COX-2 expression in lung cancer A549 cells. Mol Med Rep, 2011,4(1):25–29

    CAS  PubMed  Google Scholar 

  17. Xiao D, Powolny AA, Moura MB, et al. Phenethyl isothiocyanate inhibits oxidative phosphorylation to trigger reactive oxygen species-mediated death of human prostate cancer cells. J Biol Chem, 2010,285(34):26 558–26 569

    Article  CAS  Google Scholar 

  18. Zhu Q, Wang J, Zhang Y, et al. Mechanisms of MPP(+)-induced PC12 cell apoptosis via reactive oxygen species. J Huazhong Univ Sci Technolog Med Sci, 2012,32(6):861–866

    CAS  PubMed  Google Scholar 

  19. Xiao D, Powolny AA, Singh SV. Benzyl isothiocyanate targets mitochondrial respiratory chain to trigger reactive oxygen species-dependent apoptosis in human breast cancer cells. J Biol Chem, 2008,283(44):30 151–30 163

    Article  CAS  Google Scholar 

  20. Oltersdorf T, Elmore SW, Shoemaker AR, et al. An inhibitor of Bcl-2 family proteins induces regression of solid tumors. Nature, 2005,435(7042):677–681

    Article  CAS  PubMed  Google Scholar 

  21. Metrailler-Ruchonnet I, Pagano A, Carnesecchi S, et al. Bcl-2 protects against hyperoxia-induced apoptosis through inhibition of the mitochondria-dependent pathway. Free Radic Biol Med, 2007,42(7):1062–1074

    Article  CAS  PubMed  Google Scholar 

  22. Yang HL, Chen CS, Chang WH, et al. Growth inhibition and induction of apoptosis in MCF-7 breast cancer cells by Antrodia camphorata. Cancer Lett, 2006,231(2):215–227

    Article  CAS  PubMed  Google Scholar 

  23. Yao Y, Huang C, Li ZF, et al. Exogenous phosphatidylethanolamine induces apoptosis of human hepatoma HepG2 cells via the bcl-2/bax pathway. World J Gastroenterol, 2009,15(14):1751–1758

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Jiang TS, Zhou LP, Zhang WL, et al. Effects of sinomenine on proliferation and apoptosis in human lung cancer cell line NCI-H460 in vitro. Mol Med Rep, 2010,3(1):51–56

    CAS  PubMed  Google Scholar 

  25. Gen G, Zhao YP, Yang L, et al. Anti-proliferative effect of clitocine from the mushroom Leucopaxillus giganteus on human cervical cancer HeLa cells by inducing apoptosis. Cancer Lett, 2008,262(2):190–200

    Article  Google Scholar 

  26. Fuster JJ, Sanz-Gonzalez SM, Moll UM, et al. Classic and novel roles of p53: prospects for anticancer therapy. Trends Mol Med, 2007,13(5):192–199

    Article  CAS  PubMed  Google Scholar 

  27. Park KR, Nam D, Yun HM, et al. beta-Caryophyllene oxide inhibits growth and induces apoptosis through the suppression of PI3K/AKT/mTOR/S6K1 pathways and ROS-mediated MAPKs activation. Cancer Lett, 2011,312(2):178–188

    Article  CAS  PubMed  Google Scholar 

  28. Zhu JF, Li ZJ, Zhang GS, et al. Icaritin shows potent anti-leukemia activity on chronic myeloid leukemia in vitro and in vivo by regulating MAPK/ERK/JNK and JAK2/STAT3/AKT signalings. PLoS One, 2011,6(8):e23720

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Authors and Affiliations

  1. The Genetic Engineering International Cooperation Base of Chinese Ministry of Science and Technology, Key Laboratory of Molecular Biophysics of Chinese Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China

    Qian Zheng  (郑 倩), Wei-wei Liu  (刘伟伟), Bin Li  (李 斌), Hui-jie Chen  (陈慧洁), Wen-shan Zhu  (祝文山), Guang-xiao Yang  (杨广笑), Ming-jie Chen  (陈明洁) & Guang-yuan He  (何光源)

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  1. Qian Zheng  (郑 倩)
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  2. Wei-wei Liu  (刘伟伟)
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  3. Bin Li  (李 斌)
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  4. Hui-jie Chen  (陈慧洁)
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  5. Wen-shan Zhu  (祝文山)
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  6. Guang-xiao Yang  (杨广笑)
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  7. Ming-jie Chen  (陈明洁)
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  8. Guang-yuan He  (何光源)
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Corresponding authors

Correspondence to Ming-jie Chen  (陈明洁) or Guang-yuan He  (何光源).

Additional information

This project was supported by grants from Wuhan Municipal Science and Technology Research Project, China (No. 201260523185), and the Public Science and Technology Research Funds Projects of Ocean, China (No. 201005013).

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Zheng, Q., Liu, Ww., Li, B. et al. Anticancer effect of icaritin on human lung cancer cells through inducing s phase cell cycle arrest and apoptosis. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 34, 497–503 (2014). https://doi.org/10.1007/s11596-014-1305-1

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  • DOI: https://doi.org/10.1007/s11596-014-1305-1

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