Tumor Biology

, Volume 36, Issue 4, pp 2907–2912 | Cite as

Polygala tenuifolia polysaccharide (PTP) inhibits cell proliferation by repressing Bmi-1 expression and downregulating telomerase activity

  • Fubin Zhang
  • Xiaowei Song
  • Li Li
  • Jingfang Wang
  • Leyuan Lin
  • Cong Li
  • Hongtao Li
  • Yanju Lv
  • Yinghua Jin
  • Ying Liu
  • Yu Hu
  • Tao Xin
Research Article

Abstract

In our previous study, we isolated a homogeneous polysaccharide (PTP) with antitumor activity from the roots of Polygala tenuifolia. In view of the close correlation between Bmi-1 expression and progression of ovarian cancer, we intend to elucidate the mechanism of its activity by determining the Bmi-1 expression and the telomerase activity in human ovarian carcinoma OVCAR-3 cells following treatment with PTP at three concentrations of 0.5, 1, and 2 mg/mL for 48 h. MTT and colony-forming assays revealed that PTP had a significant inhibitory effect on the cell growth and colony formation of OVCAR-3 cells. Furthermore, Western blot and real-time PCR analysis showed that PTP inhibited Bmi-1 both in protein and transcript levels. Besides, the telomerase activity in OVCAR-3 cells was also downregulated after PTP treatment for 48 h. Taken together, the inhibitory effect of PTP on the cell growth was at least in part mediated via the downregulation of Bmi-1 expression and the telomerase activity in OVCAR-3 cells, and PTP might be a new candidate for chemotherapeutic agent against human ovarian cancer.

Keywords

Polygala tenuifolia Polysaccharide Human ovarian cancer Bmi-1 Telomerase Antitumor 

Notes

Acknowledgments

This research is funded by the Doctoral Research Fund of the Second Affiliated Hospital of Harbin Medical University (Harbin, China).

Conflicts of interest

None.

References

  1. 1.
    Sankaranarayanan R, Ferlay J. Worldwide burden of gynaecological cancer: the size of the problem. Best Pract Res Clin Obstet Gynaecol. 2005;20:207–25.CrossRefPubMedGoogle Scholar
  2. 2.
    Guppy AE, Nathan PD, Rustin GJ. Epithelial ovarian cancer: a review of current management. Clin Oncol (R Coll Radiol). 2005;17:399–411.CrossRefGoogle Scholar
  3. 3.
    Badgwell D, Bast RJ. Early detection of ovarian cancer. Dis Markers. 2007;23:397–410.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Bast Jr RC, Brewer M, Zou C, Hernandez MA, Daley M, Ozols R, et al. Prevention and early detection of ovarian cancer: mission impossible? Recent Results Cancer Res. 2007;174:91–100.CrossRefPubMedGoogle Scholar
  5. 5.
    Silva JS, Moura MD, Oliveira RA, Diniz MF, Barbosa-Filho JM. Natural product inhibitors of ovarian neoplasia. Phytomedicine. 2003;10:221–32.CrossRefPubMedGoogle Scholar
  6. 6.
    Brewer MA, Johoson K, Follen M, Gershenson D, Bast Jr R. Prevention of ovarian cancer: intraepithelial neoplasia. Clin Cancer Res. 2003;9:20–30.PubMedGoogle Scholar
  7. 7.
    Westfall SD, Nilsson EE, Skinner MK. Role of triptolide as an adjunct chemotherapy for ovarian cancer. Chemotherapy. 2008;54:67–76.CrossRefPubMedGoogle Scholar
  8. 8.
    Carr C, Ng J, Wigmore T. The side effects of chemotherapeutic agents. Curr Anaesth Crit Care. 2008;19:70–9.CrossRefGoogle Scholar
  9. 9.
    Kim E, Rye PT, Essigmann JM, Croy RG. A bifunctional platinum (II) antitumor agent that forms DNA adducts with affinity for the estrogen receptor. J Inorg Biochem. 2009;103:256–61.CrossRefPubMedGoogle Scholar
  10. 10.
    Lee MM, Lin SS, Wrensch MR, Adler SR, Eisenberg D. Alternative therapies used by women with breast cancer in four ethnic populations. J Natl Cancer Inst. 2000;92:42–7.CrossRefPubMedGoogle Scholar
  11. 11.
    Cui Y, Shu XO, Gao Y, Wen W, Ruan ZX, Jin F, et al. Use of complementary and alternative medicine by Chinese women with breast cancer. Breast Cancer Res Treat. 2004;85:263–70.CrossRefPubMedGoogle Scholar
  12. 12.
    Powell CB, Dibble SL, Dall’Era JE, Cohen I. Use of herbs in women diagnosed with ovarian cancer. Int J Gynecol Cancer. 2002;12:214–7.CrossRefPubMedGoogle Scholar
  13. 13.
    Wirth JH, Hudgins JC, Paice JA. Use of herbal therapies to relieve pain: a review of adverse effects. Pain Manag Nurs. 2005;6:145–67.CrossRefPubMedGoogle Scholar
  14. 14.
    Zhu W, Huang L, Xu X, Qian H, Xu W. Anti-proliferation effect of BMI-1 in U937 cells with siRNA. Int J Mol Med. 2010;25:889–95.CrossRefPubMedGoogle Scholar
  15. 15.
    Becker M, Korn C, Sienerth AR, Voswinckel R, Luetkenhaus K, Ceteci F, et al. Polycomb group protein Bmi1 is required for growth of RAF driven non-small-cell lung cancer. PLoS One. 2009;4:4230.CrossRefGoogle Scholar
  16. 16.
    Sawa M, Yamamoto K, Yokozawa T, Kiyoi H, Hishida A, Kajiguchi T, et al. BMI-1 is highly expressed in M0-subtype acute myeloid leukemia. Int J Hematol. 2005;82:42–7.CrossRefPubMedGoogle Scholar
  17. 17.
    Beà S, Tort F, Pinyol M, Puig X, Hernández L, Hernández S, et al. BMI-1 gene amplification and overexpression in hematological malignancies occur mainly in mantle cell lymphomas. Cancer Res. 2001;61:2409–12.PubMedGoogle Scholar
  18. 18.
    Kim JH, Yoon SY, Jeong SH, Kim SY, Moon SK, Joo JH. Overexpression of Bmi-1 oncoprotein correlates with axillary lymph node metastases in invasive ductal breast cancer. Breast. 2004;13:383–8.CrossRefPubMedGoogle Scholar
  19. 19.
    Kim JH, Yoon SY, Kim CN, Joo JH, Moon SK, Choe IS, et al. The Bmi-1 oncoprotein is overexpressed in human colorectal cancer and correlates with the reduced p16INK4a/p14ARF proteins. Cancer Lett. 2004;203:217–24.CrossRefPubMedGoogle Scholar
  20. 20.
    Song LB, Zeng MS, Liao WT, Zhang L, Mo HY, Liu WL, et al. Bmi-1 is a novel molecular marker of nasopharyngeal carcinoma progression and immortalizes primary human nasopharyngeal epithelial cells. Cancer Res. 2006;66:6225–32.CrossRefPubMedGoogle Scholar
  21. 21.
    Mihic-Probst D, Kuster A, Kilgus S, Bode-Lesniewska B, Ingold-Heppner B, Leung C, et al. Consistent expression of the stem cell renewal factor BMI-1 in primary and metastatic melanoma. Int J Cancer. 2007;121:1764–70.CrossRefPubMedGoogle Scholar
  22. 22.
    Kang MK, Kim RH, Kim SJ, Yip FK, Shin KH, Dimri GP, et al. Elevated Bmi-1 expression is associated with dysplastic cell transformation during oral carcinogenesis and is required for cancer cell replication and survival. Br J Cancer. 2007;96:126–33.CrossRefPubMedGoogle Scholar
  23. 23.
    Glinsky GV, Berezovska O, Glinskii AB. Microarray analysis identifies a death from cancer signature predicting therapy failure in patients with multiple types of cancer. J Clin Invest. 2005;115:1503–21.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Zhang F, Sui L, Xin T. Correlations of BMI-1 expression and telomerase activity in ovarian cancer tissues. Exp Oncol. 2008;30:70–4.PubMedGoogle Scholar
  25. 25.
    Berezovska OP. Essential role for activation of the Polycomb group (PcG) protein chromatin silencing pathway in metastatic prostate cancer. Cell Cycle. 2006;5:1886–901.CrossRefPubMedGoogle Scholar
  26. 26.
    Huang ST, Wang CY, Yang RC, Chu CJ, Wu HT, Pang JH. Wogonin, an active compound in Scutellaria baicalensis, induces apoptosis and reduces telomerase activity in the HL-60 leukemia cells. Phytomedicine. 2010;17:47–54.CrossRefPubMedGoogle Scholar
  27. 27.
    Park SE, Park C, Kim SH, Hossain MA, Kim MY, Chung HY, et al. Korean red ginseng extract induces apoptosis and decreases telomerase activity in human leukemia cells. J Ethnopharmacol. 2009;121:304–12.CrossRefPubMedGoogle Scholar
  28. 28.
    Xin T, Zhang FB, Sui GJ, Jin XM. Bmi-1 siRNA inhibited ovarian cancer cell line growth and decreased telomerase activity. Br J Biomed Sci. 2012;6:62–6.Google Scholar
  29. 29.
    Xin T, Zhang F, Jiang Q, Chen C, Huang D, Li Y, et al. Extraction, purification and antitumor activity of a water-soluble polysaccharide from the roots of Polygala tenuifolia. Carbohydr Polym. 2012;90:1127–31.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Fubin Zhang
    • 1
  • Xiaowei Song
    • 2
  • Li Li
    • 2
  • Jingfang Wang
    • 2
  • Leyuan Lin
    • 3
  • Cong Li
    • 4
  • Hongtao Li
    • 5
  • Yanju Lv
    • 2
  • Yinghua Jin
    • 2
  • Ying Liu
    • 2
  • Yu Hu
    • 2
  • Tao Xin
    • 2
  1. 1.Department of Gynecology, The Third Affiliated (Tumor) HospitalHarbin Medical UniversityHarbinChina
  2. 2.Department of Medical Oncology, The Second Affiliated HospitalHarbin Medical UniversityHarbinChina
  3. 3.The 209 Hospital of People’s Liberation Army (PLA)MudanjiangChina
  4. 4.Department of Pathology, The Third Affiliated (Tumour) HospitalHarbin Medical UniversityHarbinChina
  5. 5.Department of Molecular MedicineMayo ClinicRochesterUSA

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