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Anti-proliferative Effects of Atractylis lancea (Thunb.) DC. via Down-regulation of the c-myc/hTERT/Telomerase Pathway in Hep-G2 Cells

  • Guo, Wei-Qiang (School of Chemistry, Biology and Material Engineering, Suzhou University of Science and Technology) ;
  • Li, Liang-Zhi (School of Chemistry, Biology and Material Engineering, Suzhou University of Science and Technology) ;
  • He, Zhuo-Yang (School of Chemistry, Biology and Material Engineering, Suzhou University of Science and Technology) ;
  • Zhang, Qi (School of Chemistry, Biology and Material Engineering, Suzhou University of Science and Technology) ;
  • Liu, Jia (School of Chemistry, Biology and Material Engineering, Suzhou University of Science and Technology) ;
  • Hu, Cui-Ying (School of Chemistry, Biology and Material Engineering, Suzhou University of Science and Technology) ;
  • Qin, Fen-Ju (School of Chemistry, Biology and Material Engineering, Suzhou University of Science and Technology) ;
  • Wang, Tao-Yun (School of Chemistry, Biology and Material Engineering, Suzhou University of Science and Technology)
  • Published : 2013.11.30

Abstract

Atractylis lancea (Thunb.) DC. (AL), an important medicinal herb in Asia, has been shown to have anti-tumor effects on cancer cells, but the involved mechanisms are poorly understood. This study focused on potential effects and molecular mechanisms of AL on the proliferation of the Hep-G2 liver cancer cell line in vitro. Cell viability was assessed by MTT test in Hep-G2 cells incubated with an ethanol extract of AL. Then, the effects of AL on apoptosis and cell cycle progression were determined by flow cytometry. Telomeric repeat amplification protocol (TRAP) assays was performed to investigate telomerase activity. The mRNA and protein expression of human telomerase reverse transcriptase (hTERT) and c-myc were determined by real-time RT-PCR and Western blotting. Our results show that AL effectively inhibits proliferation in Hep-G2 cells in a concentrationand time-dependent manner. When Hep-G2 cells were treated with AL after 48h,the $IC_{50}$ was about 72.1 ${\mu}g/mL$. Apoptosis was induced by AL via arresting the cells in the G1 phase. Furthermore, AL effectively reduced telomerase activity through inhibition of mRNA and protein expression of hTERT and c-myc. Hence, these data demonstrate that AL exerts anti-proliferative effects in Hep-G2 cells via down-regulation of the c-myc/hTERT/telomerase pathway.

Keywords

References

  1. Cerni C (2000). Telomeres, telomerase, and myc. An update. Mutat Res, 462, 31-47. https://doi.org/10.1016/S1383-5742(99)00091-5
  2. Dang CV (2012). MYC on the path to cancer. Cell, 149, 22-35. https://doi.org/10.1016/j.cell.2012.03.003
  3. Donate LE, Blasco MA (2011). Telomeres in cancer and ageing. Phli Trans Soc B, 366, 76-84. https://doi.org/10.1098/rstb.2010.0291
  4. Fabregat I (2009). Dysregulation of apoptosis in hepatocellular carcinoma cells. World J Gastroenterol, 15, 513-20. https://doi.org/10.3748/wjg.15.513
  5. Feo F, Frau M, Pascale RM (2008). Interaction of major genes predisposing to hepatocellular carcinoma with genes encoding signal transduction pathways influences tumor phenotype and prognosis. World J Gastroenterol, 14, 6601-15. https://doi.org/10.3748/wjg.14.6601
  6. Henriksson M, Luscher B (1996). Proteins of the Myc network: essential regulators of cell growth and differentiation. Adv Cancer Res, 68, 109-82. https://doi.org/10.1016/S0065-230X(08)60353-X
  7. Huang ST, Pang JH, Yang RC (2010). Anti-cancer effects of phyllanthus urinaria and relevant mechanisms. Chang Guang Med J, 33, 477-87.
  8. Kang TH, Bang JY, Kim MH, et al (2011). Atractylenolide , a sesquiterpenoid, induces apoptosis in human lung carcinoma A549 cells via mitochondria mediated death pathway. Food Chem Toxicol, 49,514-9. https://doi.org/10.1016/j.fct.2010.11.038
  9. Liu Y, Chen W, Zeng M, et al (2012). Pharmacodynamics of water extracts from Atractylodes lancea before and after processing. Zhongguo Zhong Yao Za Zhi, 37, 2276-9.
  10. Mahavorasirikul M, Viyanant V, Chaijaroenkul W, et al (2010). Cytotoxic activity of Thai medicinal plants against human cholangiocinoma, laryngeal and hepatocarcinoma cells in vitro. BMC Complement Altern Med, doi, 10. 1186/ 1472-6882-10-55. https://doi.org/10.1186/1472-6882-10-55
  11. Mok TS, Yeo W, Johnson PJ, et al (2007). A double blind placebo-controlled randomized study of Chinese herbal medicine as complementary therapy for reduction of chemotherapy induced toxicity. Ann Oncol, 18, 768-74.
  12. Moyzis RK, Buckingham JM, Cram LS, et al (1988). A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes. Proc Natl Acad Sci USA, 85, 6622-6. https://doi.org/10.1073/pnas.85.18.6622
  13. Murnane JP (2010). Telomere loss as a mechanism for chromosome instability in human cancer. Cancer Res, 70, 4255-9. https://doi.org/10.1158/0008-5472.CAN-09-4357
  14. Ohyashiki K, Ohyashiko JH, Yahata N, et al (1997). Detection of telomerase activity and its clinical application. Rinsho Byori, 45, 1133-41.
  15. Ouellette MM, Wright WE, Shay JW (2011). Targeting telomerase expressiong cancer cells. J Cell Mol Med, 15, 1433-42. https://doi.org/10.1111/j.1582-4934.2011.01279.x
  16. Park SE, Yoo HS, Jin CY, et al (2009). Induction of apoptosis and inhibition of tolemerase activity in human lung carcinoma cells by the water extract of cordyceps militaris. Food Chem Toxicol, 47, 1667-75. https://doi.org/10.1016/j.fct.2009.04.014
  17. Peng HS, Yuan QJ, Li QQ, et al (2012). Molecular systematics of genus atractylodes (compositae, Cardueae): Evidence from internal transcribed spacer (ITS) and trnL-F sequences. Int J Mol Sci, 13, 14623-33. https://doi.org/10.3390/ijms131114623
  18. Shay JW, Wright WE (2011). Role of telomeres and telomerase in cancer. Semin Cancer Biol, 21, 349-54. https://doi.org/10.1016/j.semcancer.2011.10.001
  19. Sprouse AA, Steding CE, Herbert BS (2012). Pharmaceutical regualtion of telomerase and its clinical potential. J Cell Mol Med, 16, 1-7. https://doi.org/10.1111/j.1582-4934.2011.01460.x
  20. Ward PS, Thompson CB (2012). Metabolic reprogramming: a cancer hallmark even warburg did not anticipate. Cancer Cell, 21, 297-308. https://doi.org/10.1016/j.ccr.2012.02.014
  21. Wu KJ, Grandori C, Amacker M, et al (1999). Direct activation of TERT transcription by c-myc. Nat Genet, 21, 220-4. https://doi.org/10.1038/6010
  22. Ye Y, Wang H, Chu JH, et al (2011). Atractylenolide Ⅱ induces G1 cell-cycle arrest and apoptosis in B16 melanoma cells. J Ethnopharmacol, 136, 279-82. https://doi.org/10.1016/j.jep.2011.04.020
  23. Zhao M, Wang Q, Ouyang Z, et al (2013). Selective fraction of Atractylodes lancea (Thunb.) DC. And its growth inhibitory effect on human gastric cancer cells. Cytotechnology, doi:10.1007/s/10616-013-9559-1.
  24. Zhao Y, Jian W, Gao W, et al (2013). RNAi silencing of c-myc inhibits cell migration, invasion, and proliferation in HepG2 human hepatocellular carcinoma cell line: c-myc silencing in hepatocellular carcinoma cell. Cancer Cell Int, 13, 23-8. https://doi.org/10.1186/1475-2867-13-23

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