Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Suppressive Effect of Sinomenine Combined with 5-Fluorouracil on Colon Carcinoma Cell Growth

  • Zhang, Ji-Xiang (Department of Gastroenterology, Renmin Hospital of Wuhan University, Key Laboratory of Hubei Province for Digestive System Disease) ;
  • Yang, Zi-Rong (Department of Gastroenterology, Renmin Hospital of Wuhan University, Key Laboratory of Hubei Province for Digestive System Disease) ;
  • Wu, Dan-Dan (Department of Gastroenterology, Renmin Hospital of Wuhan University, Key Laboratory of Hubei Province for Digestive System Disease) ;
  • Song, Jia (Department of Gastroenterology, Renmin Hospital of Wuhan University, Key Laboratory of Hubei Province for Digestive System Disease) ;
  • Guo, Xu-Feng (Department of Gastroenterology, Renmin Hospital of Wuhan University, Key Laboratory of Hubei Province for Digestive System Disease) ;
  • Wang, Jing (Department of Gastroenterology, Renmin Hospital of Wuhan University, Key Laboratory of Hubei Province for Digestive System Disease) ;
  • Dong, Wei-Guo (Department of Gastroenterology, Renmin Hospital of Wuhan University, Key Laboratory of Hubei Province for Digestive System Disease)
  • Published : 2014.08.30
Download PDF
⟨ Previous Next ⟩

Abstract

It is reported that sinomenine (SIN) and 5-fluorouracil (5-FU) both are effective for colon cancer, but their cooperative suppressive effects and toxicity remain to be clarified in detail. This study aimed to determine suppressive effects and toxicity of sinomenine (SIN) plus 5-fluorouracil (5-FU) on LoVo colon carcinoma cells in vitro and in vivo. CCK-8, Hoechst 33258 staining and an annexin V-FITC/PI apoptosis kit were used to detect suppressive effects. Western blotting was applied to investigate the essential mechanism underlying SIN and 5-FU-induced apoptosis. SIN or 5-FU or both were injected into nude mice, and then suppressive effects and side effects were observed. SIN plus 5-FU apparently inhibited the proliferation of LoVo cells and induced apoptosis. Moreover the united effects were stronger than individually (p<0.05). The results of annexin V-FITC/PI staining and Hoechst 33258 staining showed that the percentage of apoptotic cells induced by SIN and 5-FU combined or alone was significantly higher than the control group (p<0.05). Expression of Bax and Bcl-2 was up-regulated and down-regulated respectively. SIN or 5-FU significantly inhibited effects on the volume of tumour xenografts and their combined suppressive effects were stronger (p<0.05). No obvious side effects were observed. It was apparent that the united effects of SIN and 5-FU on the growth of colorectal carcinoma LoVo cells in vitro and in vivo were superior to those using them individually, and it did not markedly increase the side effects of chemotherapy.

Keywords

References

  1. Baba H, Hayashi N, Emi Y, et al (2011). A multicenter phase II clinical study of oxaliplatin, folinic acid, and 5-fluorouracil combination chemotherapy as first-line treatment for advanced colorectal cancer: a Japanese experience. Surg Today, 41, 1610-6. https://doi.org/10.1007/s00595-011-4589-9
  2. Beretta GD, Milesi L, Pessi MA, et al (2004). Adjuvant treatment of colorectal cancer. Surg Oncol, 13, 63-73. https://doi.org/10.1016/j.suronc.2004.09.008
  3. Center MM, Jemal A, Ward E (2009). International trends in colorectal cancer incidence rates. Cancer Epidemiol Biomarkers Prev, 18, 1688-94. https://doi.org/10.1158/1055-9965.EPI-09-0090
  4. Chen DP, Wong CK, Leung PC, et al (2011). Anti-inflammatory activities of Chinese herbal medicine sinomenine and Liang Miao San on tumor necrosis factor-alpha-activated human fibroblast-like synoviocytes in rheumatoid arthritis. J Ethnopharmacol, 137, 457-68. https://doi.org/10.1016/j.jep.2011.05.048
  5. Chen M, Wang J (2002). Initiator caspases in apoptosis signaling pathways. Apoptosis, 7, 313-9. https://doi.org/10.1023/A:1016167228059
  6. Di Lena M, Travaglio E, Altomare DF (2013). New strategies for colorectal cancer screening. World J Gastroenterol, 19, 1855-60. https://doi.org/10.3748/wjg.v19.i12.1855
  7. Focan C, Kreutz F, Graas MP, et al (2013). Phase I - II study to assess the feasibility and activity of the triple combination of 5-fluorouracil/folinic acid, carboplatin and irinotecan (CPT-11) administered by chronomodulated infusion for the treatment of advanced colorectal cancer. Final report of the BE-1603 study. Pathol Biol (Paris), 61, 27-31. https://doi.org/10.1016/j.patbio.2010.12.005
  8. Ghiringhelli F, Bruchard M, Apetoh L (2013). Immune effects of 5-fluorouracil: Ambivalence matters. Oncoimmunology, 2, 23139. https://doi.org/10.4161/onci.23139
  9. Green DR (2005). Apoptotic pathways: ten minutes to dead. Cell, 121, 671-4. https://doi.org/10.1016/j.cell.2005.05.019
  10. Hakim L, Alias E, Makpol S, et al (2014). Gelam honey and ginger potentiate the anti cancer effect of 5-FU against HCT 116 colorectal cancer cells. Asian Pac J Cancer Prev, 15, 4651-7. https://doi.org/10.7314/APJCP.2014.15.11.4651
  11. He X, Wang J, Guo Z, et al (2005). Requirement for ERK activation in sinomenine-induced apoptosis of macrophages. Immunol Lett, 98, 91-6. https://doi.org/10.1016/j.imlet.2004.10.027
  12. Huang J, Lin Z, Luo M, et al (2007). Sinomenine suppresses TNF-alpha-induced VCAM-1 expression in human umbilical vein endothelial cells. J Ethnopharmacol, 114, 180-5. https://doi.org/10.1016/j.jep.2007.07.036
  13. Ikebukuro K, Adachi Y, Toki J, et al (2000). Morphological change, loss of deltapsi (m) and activation of caspases upon apoptosis of colorectal adenocarcinoma induced by 5-FU. Cancer Lett, 153, 101-8. https://doi.org/10.1016/S0304-3835(00)00384-0
  14. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90. https://doi.org/10.3322/caac.20107
  15. Jemal A, Siegel R, Xu J, et al (2010). Cancer statistics, 2010. CA Cancer J Clin, 60, 277-300. https://doi.org/10.3322/caac.20073
  16. Jiang T, Zhou L, Zhang W, et al (2007) Sinomenine promotes differentiation but impedes maturation and co-stimulatory molecule expression of human monocyte-derived dendritic cells. Int Immunopharmacol, 7, 1102-10. https://doi.org/10.1016/j.intimp.2007.04.007
  17. Jiang T, Zhou L, Zhang W, et al (2010). Effects of sinomenine on proliferation and apoptosis in human lung cancer cell line NCI-H460 in vitro. Mol Med Report, 3, 51-6.
  18. Ju XD, Deng M, Ao YF, et al (2010). Protective effect of sinomenine on cartilage degradation and chondrocytes apoptosis. Yakugaku Zasshi, 130, 1053-60. https://doi.org/10.1248/yakushi.130.1053
  19. Kasibhatla S, Tseng B (2003). Why target apoptosis in cancer treatment? Mol Cancer Ther, 2, 573-80.
  20. Kok TW, Yue PY, Mak NK, et al (2005). The anti-angiogenic effect of sinomenine. Angiogenesis, 8, 3-12. https://doi.org/10.1007/s10456-005-2892-z
  21. Labianca R, Beretta GD, Kildani B, et al (2010). Colon cancer. Crit Rev Oncol Hematol, 74, 106-33. https://doi.org/10.1016/j.critrevonc.2010.01.010
  22. Li L, Gao XL, Ding BX (2008). Gao and B.X. Ding, Inhibitory effect of sinomenine on H2O2-induced apoptosis in neonatal rat cardiomyocytes. Zhongguo Zhong Yao Za Zhi, 33, 939-41, 961.
  23. Magesh V, Lee JC, Ahn KS, et al (2009). Ocimum sanctum induces apoptosis in A549 lung cancer cells and suppresses the in vivo growth of Lewis lung carcinoma cells. Phytother Res, 23, 1385-91. https://doi.org/10.1002/ptr.2784
  24. Matsuhashi N, Saio M, Matsuo A, et al (2005). The evaluation of gastric cancer sensitivity to 5-FU/CDDP in terms of induction of apoptosis: time- and p53 expressiondependency of anti-cancer drugs. Oncol Rep, 14, 609-15.
  25. Shu L, Yin W, Zhang J, et al (2007). Sinomenine inhibits primary CD4+ T-cell proliferation via apoptosis. Cell Biol Int, 31, 784-9. https://doi.org/10.1016/j.cellbi.2007.01.035
  26. Siegal R, Naishadham D, Jemal A (2013). Cancer Statistics 2013. CA Cancer J Clin, 63, 11-30. https://doi.org/10.3322/caac.21166
  27. Siegel R, Naishadham D, Jemal A (2012). Cancer statistics, 2012. CA Cancer J Clin, 62, 10-29. https://doi.org/10.3322/caac.20138
  28. Song J, Bi H, Xie X, et al (2013). Preparation and evaluation of sinomenine hydrochloride in situ gel for uveitis treatment. Int Immunopharmacol, 17, 99-107. https://doi.org/10.1016/j.intimp.2013.05.020
  29. Tang XY, Zhu YQ, Tao WH, et al (2007). Synergistic effect of triptolide combined with 5-fluorouracil on colon carcinoma. Postgrad Med J, 83, 338-43. https://doi.org/10.1136/pgmj.2006.055426
  30. Teng P, Liu HL, Zhang L, et al (2012). Synthesis and biological evaluation of novel sinomenine derivatives as antiinflammatory agents. Eur J Med Chem, 50, 63-74. https://doi.org/10.1016/j.ejmech.2012.01.036
  31. Unal OU, Oztop I, Unek IT, et al (2013). Two-week combination chemotherapy with gemcitabine, high-dose folinic acid and 5 fluorouracil (GEMFUFOL) as first-line treatment of metastatic biliary tract cancers. Asian Pac J Cancer Prev, 14, 5263-7. https://doi.org/10.7314/APJCP.2013.14.9.5263
  32. Waxman DJ, Schwartz PS, et al. (2003) Harnessing apoptosis for improved anticancer gene therapy. Cancer Res, 63, 8563-72.
  33. Wu XX, Kakehi Y, Mizutani Y, et al (2001). Activation of caspase-3 in renal cell carcinoma cells by anthracyclines or 5-fluorouracil. Int J Oncol, 19, 19-24.
  34. Wu Y, Wei ZW, He YL, et al (2013). Efficacy of adjuvant XELOX and FOLFOX6 chemotherapy after D2 dissection for gastric cancer. World J Gastroenterol, 19, 3309-15. https://doi.org/10.3748/wjg.v19.i21.3309
  35. Yeh KH, Yeh SH, Hsu CH, et al (2000). Prolonged and enhanced suppression of thymidylate synthase by weekly 24-h infusion of high-dose 5-fluorouracil. Br J Cancer, 83, 1510-5. https://doi.org/10.1054/bjoc.2000.1456
  36. Yi H, Lu Y, Chen JK, et al (2010) Effect of sinomenine on tumor necrosis factor-alpha and nuclear factor-kappaB in the heterotopic tissue in rats with endometriosis. Nan Fang Yi Ke Da Xue Xue Bao, 30, 1874-6.
  37. Zheng H, Shi LF, Hu JH (2007). Assessment of in vitro and in vivo recovery of sinomenine using microdialysis. Skin Res Technol, 13, 323-9. https://doi.org/10.1111/j.1600-0846.2007.00233.x
  38. Zhong C, Liu H, Jiang L, et al (2013). Chemotherapy plus best supportive care versus best supportive care in patients with non-small cell lung cancer: a meta-analysis of randomized controlled trials. PLoS One, 8, e58466. https://doi.org/10.1371/journal.pone.0058466

Cited by

  1. Recent Trends in Pharmacological Activity of Alkaloids in Animal Colitis: Potential Use for Inflammatory Bowel Disease vol.2017, pp.1741-4288, 2017, https://doi.org/10.1155/2017/8528210
  2. evaluation of 5-fluorouracil-loaded PCL nanoparticles for colon cancer treatment vol.22, pp.5, 2017, https://doi.org/10.3109/10837450.2015.1116565
  3. Sinomenine inhibits A549 human lung cancer cell invasion by mediating the STAT3 signaling pathway vol.12, pp.2, 2016, https://doi.org/10.3892/ol.2016.4768
  4. Sinomenine prevents metastasis of human osteosarcoma cells via S phase arrest and suppression of tumor-related neovascularization and osteolysis through the CXCR4-STAT3 pathway vol.48, pp.5, 2016, https://doi.org/10.3892/ijo.2016.3416
  5. Sinomenine Induces G1-Phase Cell Cycle Arrest and Apoptosis in Malignant Glioma Cells Via Downregulation of Sirtuin 1 and Induction of p53 Acetylation vol.17, pp.1533-0338, 2018, https://doi.org/10.1177/1533034618770305