Tumor Biology

, Volume 36, Issue 4, pp 2913–2919 | Cite as

Polygala tenuifolia polysaccharide PTP induced apoptosis in ovarian cancer cells via a mitochondrial pathway

  • 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


One purified polysaccharide protein tyrosine phosphatase (PTP) was isolated from the roots of Polygala tenuifolia. The aim of the present study is to investigate the antitumor effect of PTP on human ovarian cancer OVCAR-3 cells and explore the molecular mechanism of the action involved. The results of MTT assay and apoptosis detection assay showed that PTP inhibited cellular proliferation of OVCAR-3 cells and induced apoptotic cellular death via arresting cell circle at the G0/G1 phase. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis identified that bcl-2 gradually decreased at both transcription and protein levels after PTP treatment for 48 h in OVCAR-3 cells, while those of bax, cytochrome c, caspase-3, and caspase-9 increased. In addition, the low expression of NF-κB in PTP-treated OVCAR-3 cells would trigger the extrinsic pathway of programmed cell death signaling in tumor cells. These results together suggest that PTP may induce apoptosis of OVCAR-3 cells through a mitochondrial pathway.


Polygala tenuifolia Polysaccharide Apoptosis Mitochondrial Caspase Ovarian cancer 



This research is funded by the National Natural Science Foundation of China (no. 81373904) and the Doctoral Research Fund of the Second Affiliated Hospital of Harbin Medical University (Harbin, China).

Conflicts of interest



  1. 1.
    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
  2. 2.
    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
  3. 3.
    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:e4230.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    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
  5. 5.
    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
  6. 6.
    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
  7. 7.
    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
  8. 8.
    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
  9. 9.
    Hannon GJ. RNA interference. Nature. 2002;418:244–51.CrossRefPubMedGoogle Scholar
  10. 10.
    Liu L, Andrews LG, Tollefsbol TO. Loss of the human polycomb group protein BMI1 promotes cancer-specific cell death. Oncogene. 2006;25:4370–5.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    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
  12. 12.
    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
  13. 13.
    Dubois M, Gilles KA, Hamilton JK, Rebers PA, Smith F. Colorimetric method for determination of sugars and related substances. Anal Chem. 1956;28:350–6.CrossRefGoogle Scholar
  14. 14.
    Xin T, Zhang F, Jiang Q, Chen C, Huang D, Li Y, et al. The inhibitory effect of a polysaccharide from Codonopsis pilosula on tumor growth and metastasis in vitro. Int J Biol Macromol. 2012;51:788–93.CrossRefPubMedGoogle Scholar
  15. 15.
    Yan YY, Su XD, Liang YJ, Zhang JY, Shi CJ, Lu Y, et al. Emodin azide methyl anthraquinone derivative triggers mitochondrial-dependent cell apoptosis involving in caspase-8-mediated Bid cleavage. Mol Cancer Ther. 2008;7:1688–97.CrossRefPubMedGoogle Scholar
  16. 16.
    Liang M, Li SC, Shen B, Cai JP, Li C, Wang ZY, et al. Anti-hepatocarcinoma effects of Aconitum coreanum polysaccharides. Carbohydr Polym. 2012;88:973–6.CrossRefGoogle Scholar
  17. 17.
    Yang SF, Chen MK, Hsieh YS, Yang JS, Zavras AI, Hsieh YH, et al. Antimetastatic effects of Terminalia catappa L. on oral cancer via a down-regulation of metastasis-associated proteases. Food Chem Toxicol. 2010;48:1052–8.CrossRefPubMedGoogle Scholar
  18. 18.
    Harris MH, Thompson CB. The role of the Bcl-2 family in the regulation of outer mitochondrial membrane permeability. Cell Death Differ. 2012;7:1182–91.CrossRefGoogle Scholar
  19. 19.
    Micoud F, Mandrand B, Malcus-Vocanson C. Comparison of several techniques for the detection of apoptotic astrocytes in vitro. Cell Prolif. 2001;34:99–113.CrossRefPubMedGoogle Scholar
  20. 20.
    Lee EO, Lee JR, Kim KH, Baek NI, Lee SJ, Lee BH, et al. The methylene chloride fraction of Trichosanthis Fructus induces apoptosis in U937 cells through the mitochondrial pathway. Biol Pharm Bull. 2006;29:21–5.CrossRefPubMedGoogle Scholar
  21. 21.
    Liu J, Shen HM, Ong CN. Role of intracellular thiol depletion, mitochondrial dysfunction and reactive oxygen species in Salvia miltiorrhiza-induced apoptosis in human hepatoma HepG2 cells. Life Sci. 2001;69:1833–50.CrossRefPubMedGoogle Scholar
  22. 22.
    Kim KC, Kim JS, Son JK, Kim IG. Enhanced induction of mitochondrial damage and apoptosis in human leukemia HL-60 cells by the Ganoderma lucidum and Duchesnea chrysantha extracts. Cancer Lett. 2007;246:210–7.CrossRefPubMedGoogle Scholar
  23. 23.
    Tang XL, Yang XY, Jung HJ, Kim SY, Jung SY, Choi DY, et al. Asiatic acid induces colon cancer cell growth inhibition and apoptosis through mitochondrial death cascade. Biol Pharm Bull. 2009;32:1399–405.CrossRefPubMedGoogle Scholar
  24. 24.
    Liu MJ, Wang Z, Li HX, Wu RC, Liu YZ, Wu QY. Mitochondrial dysfunction as an early event in the process of apoptosis induced by woodfordin I in human leukemia K562 cells. Toxicol Appl Pharmacol. 2004;194:141–55.CrossRefPubMedGoogle Scholar
  25. 25.
    Green DR, Reed JC. Mitochondria and apoptosis. Science. 1998;281:1309–12.CrossRefPubMedGoogle Scholar
  26. 26.
    Hengartner MO. The biochemistry of apoptosis. Nature. 2000;407:770–6.CrossRefPubMedGoogle Scholar
  27. 27.
    Kumar MA, Nair M, Hema PS, Mohan J, Santhoshkumar TR. Pinocembrin triggers Bax-dependent mitochondrial apoptosis in colon cancer cells. Mol Carcinog. 2007;46:231–41.CrossRefPubMedGoogle Scholar
  28. 28.
    Yang S, Evens AM, Prachand S, Singh AT, Bhalla S, David K, et al. Mitochondrial-mediated apoptosis in lymphoma cells by the diterpenoid lactone andrographolide, the active component of Andrographis paniculata. Clin Cancer Res. 2010;16:4755–68.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Chan CK, Goh BH, Kamarudin MN, Kadir HA. Aqueous fraction of Nephelium ramboutan-ake rind induces mitochondrial-mediated apoptosis in HT-29 human colorectal adenocarcinoma cells. Molecules. 2012;17:6633–57.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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