Browse > Article
http://dx.doi.org/10.7314/APJCP.2013.14.11.6363

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)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.14, no.11, 2013 , pp. 6363-6367 More about this Journal
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
Atractylis lancea (Thunb.) DC; liver cancer; telomerase activity; hTERT; C-myc;
Citations & Related Records
연도 인용수 순위
  • Reference
1 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.   DOI   ScienceOn
2 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.
3 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.   DOI   ScienceOn
4 Murnane JP (2010). Telomere loss as a mechanism for chromosome instability in human cancer. Cancer Res, 70, 4255-9.   DOI
5 Ohyashiki K, Ohyashiko JH, Yahata N, et al (1997). Detection of telomerase activity and its clinical application. Rinsho Byori, 45, 1133-41.
6 Ouellette MM, Wright WE, Shay JW (2011). Targeting telomerase expressiong cancer cells. J Cell Mol Med, 15, 1433-42.   DOI   ScienceOn
7 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.   DOI   ScienceOn
8 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.   DOI   ScienceOn
9 Shay JW, Wright WE (2011). Role of telomeres and telomerase in cancer. Semin Cancer Biol, 21, 349-54.   DOI   ScienceOn
10 Cerni C (2000). Telomeres, telomerase, and myc. An update. Mutat Res, 462, 31-47.   DOI   ScienceOn
11 Dang CV (2012). MYC on the path to cancer. Cell, 149, 22-35.   DOI   ScienceOn
12 Donate LE, Blasco MA (2011). Telomeres in cancer and ageing. Phli Trans Soc B, 366, 76-84.   DOI   ScienceOn
13 Fabregat I (2009). Dysregulation of apoptosis in hepatocellular carcinoma cells. World J Gastroenterol, 15, 513-20.   DOI
14 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.   DOI
15 Henriksson M, Luscher B (1996). Proteins of the Myc network: essential regulators of cell growth and differentiation. Adv Cancer Res, 68, 109-82.   DOI
16 Huang ST, Pang JH, Yang RC (2010). Anti-cancer effects of phyllanthus urinaria and relevant mechanisms. Chang Guang Med J, 33, 477-87.
17 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.   DOI   ScienceOn
18 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.
19 Ward PS, Thompson CB (2012). Metabolic reprogramming: a cancer hallmark even warburg did not anticipate. Cancer Cell, 21, 297-308.   DOI   ScienceOn
20 Sprouse AA, Steding CE, Herbert BS (2012). Pharmaceutical regualtion of telomerase and its clinical potential. J Cell Mol Med, 16, 1-7.   DOI   ScienceOn
21 Wu KJ, Grandori C, Amacker M, et al (1999). Direct activation of TERT transcription by c-myc. Nat Genet, 21, 220-4.   DOI   ScienceOn
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.   DOI   ScienceOn
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.   DOI   ScienceOn