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Preventive Effect of Actinidia Valvata Dunn Extract on N-methyl-N'-nitro-N-nitrosoguanidine-induced Gastrointestinal Cancer in Rats

  • Wang, Xia (Department of Traditional Chinese Medicine, the First Affiliated Hospital of Nanjing Medical University) ;
  • Liu, Hao (Department of Traditional Chinese Medicine, the First Affiliated Hospital of Nanjing Medical University) ;
  • Wang, Xin (Nanjing Pharmaceutical Secondary Vocational School) ;
  • Zeng, Zhi (Department of Traditional Chinese Medicine, the First Affiliated Hospital of Nanjing Medical University) ;
  • Xie, Li-Qun (Department of Traditional Chinese Medicine, the First Affiliated Hospital of Nanjing Medical University) ;
  • Sun, Zhi-Guang (Nanjing University of Traditional Chinese Medicine) ;
  • Wei, Mu-Xin (Department of Traditional Chinese Medicine, the First Affiliated Hospital of Nanjing Medical University)
  • Published : 2014.08.15

Abstract

Purpose: This study was conducted to assess the preventive effect of Actinidia valvata Dunn (AVD) extract on an animal model of gastrointestinal carcinogenesis on the basis of changes in tumor incidence, cell proliferation, and apoptosis. Materials and Methods: Seventy-five male Wistar rats were divided into five different treatment groups with 15 rats in each group. Group I was given normal feed, whereas Groups II to IV were treated with 10% sodium chloride in the first six weeks and 100ug/mL of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in drinking water for 24 weeks. Group II was then given normal feed, whereas Group III was given AVD extract (0.24g/kg/day) for 12 weeks. Group IV was given AVD extract from the first week to the 36th week, whereas Group V was treated with AVD extract alone for 36 weeks. All rats were sacrificed at the end of the 36-week experiment and assessed for the presence of gastrointestinal tumors. The occurrence of cancer was evaluated by histology. Bax, Bcl-2, Caspase-3, and cyclinD1 were determined by immunohistochemical staining and Western blotting. Results: The incidences of gastric cancer were 0% in Group I, 73.3% in Group II, 33.3% in Group III, 26.7% in Group IV, and 0% in Group V. Bcl-2 and cyclinD1 expression was decreased in AVD extract treated groups, whereas Bax and Caspase-3 expression was increased. Comparison with group II revealed significant differences (p<0.01). Conclusions: AVD extract exhibits an obvious preventive effect on gastrointestinal carcinogenesis induced by MNNG in rats through the regulation of cell proliferation and apoptosis.

Keywords

References

  1. Bilici M, Cayir K, Tekin SB, et al (2012). Effect of mirtazapine on MNNG-induced gastric adenocarcinoma in rats. Asian Pac J Cancer Prev, 13, 4897-900. https://doi.org/10.7314/APJCP.2012.13.10.4897
  2. Fuccio L, Eusebi LH, Bazzoli F (2010). Gastric cancer, Helicobacter pylori infection and other risk factors. World J Gastrointest Oncol, 2, 342-7.
  3. Fujiwara Y, Takaishi K, Nakao J, et al (2013). Corosolic acid enhances the antitumor effects of chemotherapy on epithelial ovarian cancer by inhibiting signal transducer and activator of transcription 3 signaling. Oncol Lett, 6, 1619-23.
  4. Ganapathy E, Peramaiyan R, Rajasekaran D, et al (2008). Modulatory effect of naringenin on N-methyl-N'-nitro-Nnitrosoguanidine and saturated sodium chloride-induced gastric carcinogenesis in male wistar rats. Clin Exp Pharmacol Physiol, 35, 1190-6. https://doi.org/10.1111/j.1440-1681.2008.04987.x
  5. Hu PJ, Yu J, Zeng ZR, et al (2004). Chemoprevention of gastric cancer by celecoxib in rats. Gut, 53, 195-200. https://doi.org/10.1136/gut.2003.021477
  6. Ikezaki S, Nishikawa A, Furukawa F, et al (1996). Chemopreventive effects of 24R,25-dihydroxyvitamin D3, a vitamin D3 derivative, on glandular stomach carcinogenesis induced in rats by N-methyl-N'-nitro-N-nitrosoguanidine and sodium chloride. Cancer Res, 56, 2767-70.
  7. 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
  8. Lee MS, Cha EY, Thuong PT, et al (2010). Down-regulation of human epidermal growth factor receptor 2/neu oncogene by corosolic acid induces cell cycle arrest and apoptosis in NCI-N87 human gastric cancer cells. Biol Pharm Bull, 33, 931-7. https://doi.org/10.1248/bpb.33.931
  9. Li L, Ying XJ, Sun TT, et al (2012). Overview of methodological quality of systematic reviews about gastric cancer risk and protective factors. Asian Pac J Cancer Prev, 5, 2069-79. https://doi.org/10.7314/APJCP.2012.13.5.2069
  10. Lu B, Xu L, Yu LF, et al (2008). Extract of Radix Curcumae prevents gastric cancer in rats. Digestion, 77, 87-91. https://doi.org/10.1159/000122228
  11. Manikandan P, Vidjaya Letchoumy P, Prathiba D, et al (2008). Combinatorial chemopreventive effect of Azadirachta indica and Ocimum sanctum on oxidant-antioxidant status, cell proliferation, apoptosis and angiogenesis in a rat forestomach carcinogenesis model. Singapore Med J, 49, 814-22.
  12. Motohashi M, Wakui S, Muto T, et al (2011). Cyclin D1/cdk4, estrogen receptors $\alpha$ and $\beta$, in N-m ethyl-N'-nitro-N-nitrosoguanidine-induced rat gastric carcinogenesis: immunohistochemical study. J Toxicol Sci, 36, 373-8. https://doi.org/10.2131/jts.36.373
  13. Nho KJ, Chun JM, Kim HK (2013). Corosolic acid induces apoptotic cell death in human lung adenocarcinoma A549 cells in vitro. Food Chem Toxicol, 56, 8-17. https://doi.org/10.1016/j.fct.2013.02.002
  14. Okazaki K, Lshii Y, Kitamura Y, et al (2006). Dose-dependent promotion of rat forestomach carcinogenesis by combined treatment with sodium nitrite and ascorbic acid after initiation with N-methyl-N'-nitro-N-nitrosoguanidine: possible contribution of nitric oxide-associated oxidative DNA damage. Cancer Sci, 97, 175-82. https://doi.org/10.1111/j.1349-7006.2006.00162.x
  15. Priyadarsini RV, Nagini S (2012). Cancer chemoprevention by dietary phytochemicals: promises and pitfalls. Curr Pharm Biotechnol, 13, 125-36. https://doi.org/10.2174/138920112798868610
  16. Qu LP, Xin HL, Zheng GY, et al (2012). Hepatoprotective activity of the total saponins from Actinidia valvata Dunn root against carbon tetrachloride-induced liver damage in mice. Evid Based Complement Alternat Med, 216061.
  17. Qu LP, Zheng GY, Su YH, et al (2012). New triterpenoids with cytotoxic activity from Actinidia Valvata. Int J Mol Sci, 13, 14865-70. https://doi.org/10.3390/ijms131114865
  18. Rasul A, Yu B, Khan M, et al (2012). Magnolol, a natural compound, induces apoptosis of SGC-7901 human gastric adenocarcinoma cells via the mitochondrial and PI3K/Akt signaling pathways. Int J Oncol, 40, 1153-61.
  19. Sung B, Kang YJ, Kim DH, et al (2014). Corosolic acid induces apoptotic cell death in HCT116 human colon cancer cells through a caspase-dependent pathway. Int J Mol Med, 33, 943-9.
  20. Tatematsu M, Takahashi M, Fukushima S, et al (1975). Effects in rats of sodium chloride on experimental gastric cancers induced by N-methyl-N-nitro-N-nitrosoguanidine or 4-nitroquinoline-1-oxide. J Natl Cancer Inst, 55, 101-6.
  21. Tomita H, Kuno T, Yamada Y, et al (2008). Preventive effect of fermented brown rice and rice bran on N-methyl-N'-nitro-N-nitrosoguanidine-induced gastric carcinogenesis in rats. Oncol Rep, 19, 11-5.
  22. Tsao AS, Kim ES, Hong WK (2004). Chemoprevention of cancer. CA Cancer J Clin, 54, 150-80. https://doi.org/10.3322/canjclin.54.3.150
  23. Tsugane S, Sasazuki S (2007). Diet and the risk of gastric cancer: review of epidemiological evidence. Gastric Cancer, 10, 75-83. https://doi.org/10.1007/s10120-007-0420-0
  24. Tsugane S, Sasazuki S, Kobayashi M, et al (2004). Salt and salted food intake and subsequent risk of gastric cancer among middle-aged Japanese men and women. Br J Cancer, 90, 128-34. https://doi.org/10.1038/sj.bjc.6601511
  25. World Health Organization (2005). Cancer Prevention and Control. Report to the secretariat by the 58th World Health Assembly. [On-line]. http://www.who.int/cancer/eb1143/en/.
  26. Xu Q, Yang CH, Liu Q, et al (2011). Chemopreventive effect of epigallocatechin-3-gallate (EGCG) and folic acid on the N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastrointestinal cancer in rat model. J Dig Dis, 12, 181-7. https://doi.org/10.1111/j.1751-2980.2011.00494.x
  27. Xu Y, Ge R, Du J, et al (2009). Corosolic acid induces apoptosis through mitochondrial pathway and caspases activation in human cervix adenocarcinoma HeLa cells. Cancer Lett, 284, 229-37. https://doi.org/10.1016/j.canlet.2009.04.028
  28. Zheng GY, Xin HL, Xu YF, et al (2012). Total Saponin from Root of Actinidia valvata Dunn Inhibits Hepatoma 22 Growth and Metastasis In Vivo by Suppression Angiogenesis. Evid Based Complement Alternat Med, 432814
  29. Zullo A, Hassan C, Romiti A, et al (2012). Follow-up of intestinal metaplasia in the stomach: When, how and why. World J Gastrointest Oncol, 4, 30-36. https://doi.org/10.4251/wjgo.v4.i3.30

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