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Downregulation of Cdk1 and CyclinB1 Expression Contributes to Oridonin-induced Cell Cycle Arrest at G2/M Phase and Growth Inhibition in SGC-7901 Gastric Cancer Cells

  • Gao, Shi-Yong (Institute of Materia Medica, Research Center of Life Science and Environmental Science, Harbin University of Commerce, and Key Laboratory of Cancer Prevention and Anticancer Drugs of Heilongjiang Province) ;
  • Li, Jun (Institute of Materia Medica, Research Center of Life Science and Environmental Science, Harbin University of Commerce, and Key Laboratory of Cancer Prevention and Anticancer Drugs of Heilongjiang Province) ;
  • Qu, Xiao-Ying (Institute of Materia Medica, Research Center of Life Science and Environmental Science, Harbin University of Commerce, and Key Laboratory of Cancer Prevention and Anticancer Drugs of Heilongjiang Province) ;
  • Zhu, Nan (Institute of Materia Medica, Research Center of Life Science and Environmental Science, Harbin University of Commerce, and Key Laboratory of Cancer Prevention and Anticancer Drugs of Heilongjiang Province) ;
  • Ji, Yu-Bin (Institute of Materia Medica, Research Center of Life Science and Environmental Science, Harbin University of Commerce, and Key Laboratory of Cancer Prevention and Anticancer Drugs of Heilongjiang Province)
  • Published : 2014.08.15

Abstract

Background: Oridonin isolated from Rabdosia rubescens, a plant used to treat cancer in Chinese folk medicine, is one of the most important antitumor active ingredients. Previous studies have shown that oridonin has antitumor activities in vivo and in vitro, but little is known about cell cycle effects of oridonin in gastric cancer. Materials and Methods: MTT assay was adopted to detect the proliferation inhibition of SGC-7901 cells, the cell cycle was assessed by flow cytometry and protein expression by Western blotting. Results: Oridonin could inhibit SGC-7901 cell proliferation, the $IC_{50}$ being $15.6{\mu}M$, and blocked SGC-7901 cell cycling in the $G_2/M$ phase. The agent also decreased the protein expression of cyclinB1 and CDK1. Conclusions: Oridonin may inhibit SGC-7901 growth and block the cells in the $G_2/M$ phase by decreasing Cdk1 and cyclinB1 proteins.

Keywords

References

  1. Alabsi AM, Ali R, Ali AM, et al (2012). Apoptosis induction, cell cycle arrest and in vitro anticancer activity of gonothalamin in a cancer cell lines. Asian Pac J Cancer Prev, 13, 5131-6. https://doi.org/10.7314/APJCP.2012.13.10.5131
  2. Cheng Y, Qiu F, Ye YC, et al (2009). Oridonin induces G (2)/M arrest and apoptosis via activating ERK-p53 apoptotic pathway and inhibiting PTK-Ras-Raf-JNK survival pathway in murine fibrosarcoma L929 cells. Arch Biochem Biophys, 490, 70-5.
  3. Choi S, Lew KL, Xiao H, et al (2007). D, L-sulforaphaneinduced cell death in human prostate cancer cells is regulated by inhibitor of apoptosis family proteins and Apaf-1. Carcinogenesis, 28, 151-62. https://doi.org/10.1093/carcin/bgl144
  4. Choi YY, An JY, Kim HI, et al (2014). Current practice of gastric cancer treatment. Chin Med J (Engl), 127, 547-53.
  5. Cui Q, Yu JH, Wu JN, et al (2007). P53-mediated cell cycle arrest and apoptosis through a caspase-3-independent, but caspase-9-dependent pathway in oridonin-treated MCF-7 human breast cancer cells. Acta Pharmacol Sin, 28, 1057-66. https://doi.org/10.1111/j.1745-7254.2007.00588.x
  6. Diaz-Moralli S, Tarrado-Castellarnau M, Miranda A, et al (2013). Targeting cell cycle regulation in cancer therapy. Pharmacol Ther, 138, 255-71. https://doi.org/10.1016/j.pharmthera.2013.01.011
  7. Harper JW, Burton JL, Solomon MJ (2002). The anaphasepromoting complex: it's not just for mitosis any more. Genes Dev, 16, 2179-206. https://doi.org/10.1101/gad.1013102
  8. Hartwell LH, Weinert TA (1989). Checkpoints:controls that ensure the order of cell cycles events. Science, 246, 629-34. https://doi.org/10.1126/science.2683079
  9. Hsieh TC, Wijeratne EK, Liang JY, et al (2005). Differential control of growth, cell cycle progression, and expression of NF-kappa B in human breast cancer cells MCF-7, MCF-10A, and MDA-MB-231 by ponicidin and oridonin, diterpenoids from the chinese herb Rabdosia rubescens. Biochem Biophys Res Commun, 337, 224-31. https://doi.org/10.1016/j.bbrc.2005.09.040
  10. Huang XJ, Ren W, Li J, et al (2013). Anti-inflammatory and anticancer activities of ethanol extract of pendulous monkshood root in vitro. Asian Pac J Cancer Prev, 14, 3569-73. https://doi.org/10.7314/APJCP.2013.14.6.3569
  11. Hu HB, Kuang L, Zeng XM, et al (2012). Predictive value of thymidylate synthase expression in gastric cancer: a systematic review with meta-analysis. Asian Pac J Cancer Prev, 13, 261-7. https://doi.org/10.7314/APJCP.2012.13.1.261
  12. 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
  13. Kamangar F, Dores GM, Anderson WF (2006). Patterns of cancer incidence, mortality, and prevalence across five continents: Defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol, 24, 2137-50. https://doi.org/10.1200/JCO.2005.05.2308
  14. Kang N, Zhang JH, Qiu F, et al (2010). Induction of G (2)/M phase arrest and apoptosis by oridonin in human laryngeal carcinoma cells. J Nat Prod, 73, 1058-63. https://doi.org/10.1021/np9008199
  15. Li D, Wu LJ, Tashiro SI, et al (2008). Oridonin induces human epidermoid carcinoma A431 cell apoptosis through tyrosine kinase and mitochondrial pathway. J Asian Nat Prod Res, 10, 77-87. https://doi.org/10.1080/10286020701273866
  16. Liu Y, Liu JH, Chai K, et al (2013). Inhibition of c-Met promoted apoptosis, autophagy and loss of the mitochondrial transmembrane potential in oridonin-induced A549 lung cancer cells. J Pharm Pharmacol, 65, 1622-42. https://doi.org/10.1111/jphp.12140
  17. Liu YQ, Mu ZQ, You S, et al (2006). Fas/FasL signaling allows extracelluar-signal regulated kinase to regulate cytochrome c release in oridonin-induced apoptotic U937 cells. Biol Pharm Bull, 29, 1873-9. https://doi.org/10.1248/bpb.29.1873
  18. Lou HY, Zhang XM, Gao L, et al (2009). In vitro and in vivo antitumor activity of oridonin nanosuspension. Int J Pharm, 379, 181-6. https://doi.org/10.1016/j.ijpharm.2009.06.022
  19. Mahadevan D, Plummer R, Squires MS, et al (2011). A phase I pharmacokinetic and pharmacodynamic study of AT7519, a cyclin-dependent kinase inhibitor in patients with refractory solid tumors. Ann Oncol, 22, 2137-43. https://doi.org/10.1093/annonc/mdq734
  20. Malumbres M, Barbacid M (2005). Mammalian cyclindependent kinases. Trends Biochem Sci, 30, 630-41. https://doi.org/10.1016/j.tibs.2005.09.005
  21. Malumbres M, Barbacid M (2007). Cell cycle kinases in cancer. Curr Opin Genet Dev, 17, 60-5. https://doi.org/10.1016/j.gde.2006.12.008
  22. Manchado E, Guillamot M, Malumbres M (2012). Killing cells by targeting mitosis. Cell Death Differ, 19, 369-77. https://doi.org/10.1038/cdd.2011.197
  23. Mosmann T (1983). Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods, 65, 55-63. https://doi.org/10.1016/0022-1759(83)90303-4
  24. Peters JM (2002). The anaphase-promoting complex: Proteolysis in mitosis and beyond. Mol Cell, 9, 931-43. https://doi.org/10.1016/S1097-2765(02)00540-3
  25. Qi XL, Zhang DR, Xu X, et al (2012). Oridonin nanosuspension was more effective than free oridonin on G (2)/M cell cycle arrest and apoptosis in the human pancreatic cancer PANC-1 cell line. Int J Nanomedicine, 7, 1793-804.
  26. Shapiro GI (2006). Cyclin-dependent kinase pathways as targets for cancer treatment. J Clin Oncol, 24, 1770-83. https://doi.org/10.1200/JCO.2005.03.7689
  27. Shin JS, Maeng HGun, Hong SW, et al (2012). Iris nertschinskia ethanol extract differentially induces cytotoxicity in human breast cancer cells depending on AKT1/2 activity. Asian Pac J Cancer Prev, 13, 6511-6. https://doi.org/10.7314/APJCP.2012.13.12.6511
  28. Wang CJ, Zhu GJ, Yu L, et al (2013). Preparation, in vitro, and in vivo antitumor activity of folate receptor-targeted nanoliposomes containing oridonin. Drug Dev Res, 74, 43-9. https://doi.org/10.1002/ddr.21055
  29. Wang H, Ye Y, Chu JH, et al (2010). Oridonin induces G2/M cell cycle arrest and apoptosis through MAPK and p53 signaling pathways in HepG2 cells. Oncol Rep, 24, 647-51.
  30. Yang B, Wang YQ, Cheng RB (2013). Induction of cytotoxicity and apoptosis in human gastric cancer cell SGC-7901 by isovaltrate acetoxyhydrin isolated from patrinia heterophylla bunge involves a mitochondrial pathway and G2/M phase cell cycle arrest. Asian Pac J Cancer Prev, 14, 6481-6. https://doi.org/10.7314/APJCP.2013.14.11.6481
  31. Ye LH, Li WJ, Jiang XQ, et al (2012a). Study on the autophagy of prostate cancer PC-3 cells induced by oridonin. Anat Rec (Hoboken), 295, 417-22. https://doi.org/10.1002/ar.21528
  32. Ye YC, Wang HJ, Xu L, et al (2012b). Oridonin induces apoptosis and autophagy in murine fibrosarcoma L929 cells partly via NO-ERK-p53 positive-feedback loop signaling pathway. Acta Pharmacol Sin, 33, 1055-61. https://doi.org/10.1038/aps.2012.53
  33. Yu Y, Fan SM, Song JK, et al (2012). Hydroxyl radical (center dot OH) played a pivotal role in oridonin-induced apoptosis and autophagy in human epidermoid carcinoma A431 cells. Biol Pharm Bul, 35, 2148-59. https://doi.org/10.1248/bpb.b12-00405
  34. Zang LH, He H, Ye YC, et al (2012). Nitric oxide augments oridonin- induced eff erocytosis by human histocytic lymphoma U937 cells via autophagy and the NF-kappa B-COX-2-IL-1 beta pathway. Free Radic Res, 46, 1207-19. https://doi.org/10.3109/10715762.2012.700515
  35. Zhang T, Tan Y, Zhao R, et al (2013). DNA damage induced by oridonin involves cell cycle arrest at G2/M phase in human MCF-7 cells. Contemp Onco (Pozn), 17, 38-44.
  36. Zhou GB, Kang H, Wang L, et al (2007). Oridonin, a diterpenoid extracted from medicinal herbs, targets AML1-ETO fusion protein and shows potent antitumor activity with low adverse effects on t (8;21) leukemia in vitro and in vivo. Blood, 109, 3441-50. https://doi.org/10.1182/blood-2006-06-032250
  37. Zhu M, Hong D, Bao YF, et al (2013). Oridonin induces the apoptosis of metastatic hepatocellular carcinoma cells via a mitochondrial pathway. Oncol Lett, 6, 1502-6.

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