DOI QR코드

DOI QR Code

Paris polyphylla Smith Extract Induces Apoptosis and Activates Cancer Suppressor Gene Connexin26 Expression

  • Li, Fu-Rong (School of Pharmaceutical Science, Taishan Medical University) ;
  • Jiao, Peng (Institute of Basic Medical Sciences, Taishan Medical University) ;
  • Yao, Shu-Tong (Department of Pathophysiology, Taishan Medical University) ;
  • Sang, Hui (Department of Pathophysiology, Taishan Medical University) ;
  • Qin, Shu-Cun (Institute of Basic Medical Sciences, Taishan Medical University) ;
  • Zhang, Wei (School of Pharmaceutical Science, Taishan Medical University) ;
  • Zhang, Ya-Bin (Department of Pathophysiology, Taishan Medical University) ;
  • Gao, Lin-Lin (Department of Pathophysiology, Taishan Medical University)
  • Published : 2012.01.31

Abstract

Background: The inhibition of tumor cell growth without toxicity to normal cells is an important target in cancer therapy. One possible way to increase the efficacy of anticancer drugs and to decrease toxicity or side effects is to develop traditional natural products, especially from medicinal plants. Paris polyphylla Smith has shown anti-tumour effects by inhibition of tumor promotion and inducement of tumor cell apoptosis, but mechanisms are still not well understood. The present study was to explore the effect of Paris polyphylla Smith extract (PPSE) on connexin26 and growth control in human esophageal cancer ECA109 cells. Methods: The effects of PPSE on Connexin26 were examined by RT-PCR, western blot and immunofluorescence; cell growth and proliferation were examined by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay. Results: PPSE inhibited the growth and proliferation on esophageal cancer ECA109 cells, while increasing the expression of connexin26 mRNA and protein; conversely, PPSE decreased Bcl-2 and increased Bad. Conclusion: This study firstly shows that PPSE can increase connexin26 expression at mRNA and protein level, exerting anti-tumour effects on esophageal cacner ECA109 cells via inhibiting cell proliferation and inducing cell apoptosis.

References

  1. Chang CY, Huang ZN, Yu HH, et al (2008).The adjuvant effects of Antrodia camphorate extracts combined with anti-tumor agents on multidrug resistant human hepatoma cells. J Ethnopharmacol, 118, 387-95. https://doi.org/10.1016/j.jep.2008.05.001
  2. Cheung JY, Ong RC, Suen YK, et al (2005). Polyphyllin D is a potent apoptosis inducer in drug-resistant HepG2 cells. Cancer Letters, 217, 203-11. https://doi.org/10.1016/j.canlet.2004.06.042
  3. Decrock E, Vinken M, De Vuyst E, et al (2009). Connexinrelated signaling in cell death: to live or let die? Cell Death Differ, 16, 524-36. https://doi.org/10.1038/cdd.2008.196
  4. Deng S, Yu B, Hui Y, et al (1999). Synthesis of three diosgenyl saponins:dioscin, polyphyllin D, and balanitin 7. Carbohydr Res, 317, 53-62. https://doi.org/10.1016/S0008-6215(99)00066-X
  5. Fujimoto E, Sato H, Shirai S, et al (2005). Connexin32 as a tumor suppressor gene in a metastatic renal cell carcinoma cell line. Oncogene, 4, 3684-90.
  6. Gao LL, Li FR, Jiao P, et al (2011). Apoptosis of human ovarian cancer cells induced by Paris chinensis dioscin via Ca2+- mediated mitochondrion pathway. Asian Pac J Cancer Prev, 12, 1361-6.
  7. Gao LL, Li FR, Jiao P, et al (2011). Paris chinensis dioscin induces G2/M cell cycle arrest and apoptosis in human gastric cancer SGC-7901 cells. World J Gastroenterol, 17, 4389-95. https://doi.org/10.3748/wjg.v17.i39.4389
  8. Inose T, Kato H, Kimura H, et al (2009). Correlation between connexin26 expression and poor prognosis of esophageal squamous cell carcinoma. Ann Surg Oncol, 16, 1704-10. https://doi.org/10.1245/s10434-009-0443-3
  9. Lee MS, Yuet-Wa JC, Kong SK, et al (2005). Effects of polyphyllin D, a steroidal saponin in Paris polyphylla, in growth inhibition of human breast cancer cells and in xenograft. Cancer Biol Ther, 4, 1248-54. https://doi.org/10.4161/cbt.4.11.2136
  10. Li B, Yu B, Hui Y, et al (2001). An improved synthesis of the saponin, polyphyllin D. Carbohydr Res, 331, 1-7. https://doi.org/10.1016/S0008-6215(01)00014-3
  11. Liu SX, Zhang YJ, Guo HF, et al (2009). The regulatory effect of the p38 signaling pathway on valdecoxib-induced apoptosis of the Eca109 cell line. Oncol Rep, 22, 313-9.
  12. Loncarek J, Yamasaki H, Levillain P, et al (2003). The expression of the tumor suppressor gene connexin26 is not mediated by methylation in human esophageal cancer cells. Molecular Carcinogenesis, 36, 74-81. https://doi.org/10.1002/mc.10102
  13. Martin PE and Evans WH (2004). Incorporation of connexins into plasma membranes and gap junctions. Cardiovasc Res, 62, 378-87. https://doi.org/10.1016/j.cardiores.2004.01.016
  14. Singal R, Tu ZJ, Vanwert JM, et al (2000). Modulation of the connexin26 tumor suppressor gene expression throughmethylation in humanmammary epithelial cell lines. Anticancer Res, 20, 59-64. https://doi.org/10.1097/CAD.0b013e3283160fd6
  15. Oyamada M, Oyamada Y, Takamatsu T (2005). Regulation of expression. Biochim Biophys Acta, 1719, 6-23. https://doi.org/10.1016/j.bbamem.2005.11.002
  16. Saradha B, Vaithinathan S, Mathur PP (2009). Lindane induces testicular apoptosis in adult Wistar rats through the involvement of Fas-FasL and mitochondria-dependent pathways. Toxicology, 255, 131-9. https://doi.org/10.1016/j.tox.2008.10.016
  17. Shoemaker M, Hamilton B, Dairkee SH, et al (2005). In vitro anticancer activity of twelve Chinese medicinal herbs. Phytother Res, 9, 649-51.
  18. Singal R, Tu ZJ, Vanwert JM, et al (2000). Modulation of the connexin26 tumor suppressor gene expression throughmethylation in humanmammary epithelial cell lines. Anticancer Res, 20, 59-64. https://doi.org/10.1097/CAD.0b013e3283160fd6
  19. Tanaka M, Grossman HB (2004). Connexin26 induces growth suppression, apoptosis and increased efficacy of doxorubicin in prostate cancer cells. Oncol Rep, 11, 537-41.
  20. Tanaka M, Grossman HB (2001). Connexin26 gene therapy of human bladder cancer: induction of growth suppression, apoptosis, and synergy with Cisplatin. Hum Gene Ther, 12, 2225-36. https://doi.org/10.1089/10430340152710568

Cited by

  1. The Anti-Lung Cancer Activities of Steroidal Saponins of P. polyphylla Smith var. chinensis (Franch.) Hara through Enhanced Immunostimulation in Experimental Lewis Tumor-Bearing C57BL/6 Mice and Induction of Apoptosis in the A549 Cell Line vol.18, pp.10, 2013, https://doi.org/10.3390/molecules181012916
  2. Studies on Vegetative and Reproductive Ecology of Paris polyphylla Smith: A Vulnerable Medicinal Plant vol.06, pp.16, 2015, https://doi.org/10.4236/ajps.2015.616258
  3. Distribution and phytomedicinal aspects of Paris polyphylla Smith from the Eastern Himalayan Region: A review vol.5, pp.3, 2015, https://doi.org/10.5667/tang.2015.0001
  4. Chinese herbal medicines as a source of molecules with anti-enterovirus 71 activity vol.11, pp.1, 2016, https://doi.org/10.1186/s13020-016-0074-0
  5. In silico identification of anti-cancer compounds and plants from traditional Chinese medicine database vol.6, pp.1, 2016, https://doi.org/10.1038/srep25462
  6. Aqueous Extract of Paris polyphylla (AEPP) Inhibits Ovarian Cancer via Suppression of Peroxisome Proliferator-Activated Receptor-Gamma Coactivator (PGC)-1alpha vol.21, pp.6, 2016, https://doi.org/10.3390/molecules21060727