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Dryocrassin ABBA Induces Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells Through a Caspase-Dependent Mitochondrial Pathway

  • Jin, Zhe (College of Life Sciences, Northeast Agricultural University) ;
  • Wang, Wen-Fei (College of Life Sciences, Northeast Agricultural University) ;
  • Huang, Jian-Ping (College of Life Sciences, Northeast Agricultural University) ;
  • Wang, He-Meng (College of Life Sciences, Northeast Agricultural University) ;
  • Ju, Han-Xun (College of Life Sciences, Northeast Agricultural University) ;
  • Chang, Ying (College of Life Sciences, Northeast Agricultural University)
  • Published : 2016.06.01

Abstract

Background: Biological and pharmacological activities of dryocrassin ABBA, a phloroglucinol derivative extracted from Dryopteris crassirhizoma, have attracted attention. In this study, the apoptotic effect of dryocrassin ABBA on human hepatocellular carcinoma HepG2 cells was investigated. Materials and Methods: We tested the effects of dryocrassin ABBA on HepG2 in vitro by MTT, flow cytometry, real-time PCR, and Western blotting. KM male mice were used to detect the effect of dryocrassin ABBA on H22 cells in vivo. Results: Dryocrassin ABBA inhibited the growth of HepG2 cells in a concentration-dependent manner. After treatment with 25, 50, and $75{\mu}g/mL$ dryocrassin ABBA, the cell viability was 68%, 60% and 49%, respectively. Dryocrassin ABBA was able to induce apoptosis, measured by propidium iodide (PI)/annexin V-FITC double staining. The results of real-time PCR and Western ting showed that dryocrassin ABBA up-regulated p53 and Bax expression and inhibited Bcl-2 expression which led to an activation of caspase-3 and caspase-7 in the cytosol, and then induction of cell apoptosis. In vivo experiments also showed that dryocrassin ABBA treatment significantly suppressed tumor growth, without major side effects. Conclusions: Overall, these findings provide evidence that dryocrassin ABBA may induce apoptosis in human hepatocellular carcinoma cells through a caspase-mediated mitochondrial pathway.

Keywords

References

  1. Cory S, Adams JM (2002). The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer, 2, 647-56. https://doi.org/10.1038/nrc883
  2. Fulda S (2009). Caspase-8 in cancer biology and therapy. Cancer Lett, 281, 128-33. https://doi.org/10.1016/j.canlet.2008.11.023
  3. Fauzi AN, Norazmi MN, Yaacob NS (2011). Tualang honey induces apoptosis and disrupts the mitochondrial membrane potential of human breast and cervical cancer cell lines. Food Chem Toxicol, 49, 871-8. https://doi.org/10.1016/j.fct.2010.12.010
  4. Guo XZ (1992). Toxic herbal medicine dictionary. tianjin science and technology translation company.
  5. Guy M, John AH (2000). Apoptosis and cancer chemotherapy. Cell Tissue Res, 301, 143-52. https://doi.org/10.1007/s004419900160
  6. Granado-Serrano AB, Martin MA, Bravo L, at al (2006). Quercetin induces apoptosis via caspase activation, regulation of Bcl-2, and inhibition of PI-3-kinase/Akt and ERK pathways in a human hepatoma cell line (HepG2). J Nutr, 136, 2715-21. https://doi.org/10.1093/jn/136.11.2715
  7. Herr I, Debatin KM (2001). Cellular stress response and apoptosis in cancer therapy. Blood, 98, 2603-14. https://doi.org/10.1182/blood.V98.9.2603
  8. Jiang S, Zu Y, Fu Y, et al (2008). Activation of the mitochondriadriven pathway of apoptosis in human PC-3 prostate cancer cells by a novel hydrophilic paclitaxel derivative, 7-xylosyl-10-deacetylpaclitaxel. Int J Oncol, 33, 103-11.
  9. Kim YA, Choi BT, Lee YT, et al (2004). Resveratrol inhibits cell proliferation and induces apoptosis of human breast carcinoma MCF-7 cells. Oncol Rep, 11, 441-6.
  10. Kuo CT, Hsu MJ, Chen BC, et al (2008). Denbinobin induces apoptosis in human lung adenocarcinoma cells via Akt inactivation, Bad activation, and mitochondrial dysfunction. Toxicol Lett, 177, 48-58. https://doi.org/10.1016/j.toxlet.2007.12.009
  11. Kong CS, Kim JA, Yoon NY, et al (2009). Induction of apoptosis by phloroglucinol derivative from Ecklonia Cava in MCF-7 human breast cancer cells. Food Chem Toxicol, 47, 1653-8. https://doi.org/10.1016/j.fct.2009.04.013
  12. Livak KJ, Schmittgen TD (2001). Analysis of relative gene expression data using real-time quantitative PCR and the $2^{-{\Delta}{\Delta}CT}$ method. Methods, 25, 402-8. https://doi.org/10.1006/meth.2001.1262
  13. Lau AT, Wang Y, Chiu JF (2008). Reactive oxygen species: current knowledge and applications in cancer research and therapeutic. J Cell Biochem, 104, 657-67. https://doi.org/10.1002/jcb.21655
  14. Liu X, Zu YG, Fu YJ, at al (2009). Efferth, antimicrobial activity and cytotoxicity towards cancer cells of Melaleuca alternifolia (tea tree) oil. Eur Food Res Technol, 229, 247-53. https://doi.org/10.1007/s00217-009-1057-5
  15. Li J, Bian WH, Wan J, et al (2014). Curdione inhibits proliferation of MCF-7 Cells by inducing apoptosis. Asian Pac J Cancer Prev, 15, 9997-10001 https://doi.org/10.7314/APJCP.2014.15.22.9997
  16. Nicholson DW, Ali A, Thornberry NA, et al (1995). Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature, 376, 37-43. https://doi.org/10.1038/376037a0
  17. Newman DJ, Cragg GM, Snader KM (2003). Natural products as sources of new drugs over the period 1981-2002. J Nat Prod, 66, 1022-37. https://doi.org/10.1021/np030096l
  18. Nigam N, Bhui K, Prasad S, at al (2009). [6]-Gingerol induces reactive oxygen species regulated mitochondrial cell death pathway in human epidermoid carcinoma A431 cells. Chem Biol Interact, 181, 77-84. https://doi.org/10.1016/j.cbi.2009.05.012
  19. Parkin DM (2001). Global cancer statistics in the year 2000. Lancet Oncol, 2, 533-43. https://doi.org/10.1016/S1470-2045(01)00486-7
  20. Perfettini JL, Reed JC, Israel N, et al (2002). Role of Bcl-2 family members in caspase-independent apoptosis during Chlamydia infection. Infect Immun, 70, 55-61. https://doi.org/10.1128/IAI.70.1.55-61.2002
  21. Quiney C, Billard C, Salanoubat C, et al (2006). Hyperforin, a new lead compound against the progression of cancer and leukemia?. Leukemia, 20, 1519-25. https://doi.org/10.1038/sj.leu.2404301
  22. Roy MK, Thalang VN, Trakoontivakorn G, et al (2005). Mahanine, a carbazole alkaloid from Micromelum minutum, inhibits cell growth and induces apoptosis in U937 cells through a mitochondrial dependent pathway. Br J Pharmacol, 145, 145-55. https://doi.org/10.1038/sj.bjp.0706137
  23. Thomas A, Giesler T, White E (2000). P53 mediates Bcl-2 phosphorylation and apoptosis via activation of the Cdc42/ JNK1 pathway. Oncogene, 19, 5259-69. https://doi.org/10.1038/sj.onc.1203895
  24. Timmer T, de Vries EG, de Jong S (2002). Fas receptor-mediated apoptosis: a clinical application? J Pathol, 196, 125-34. https://doi.org/10.1002/path.1028
  25. Zhou YJ, Zhang SP, Liu CW, et al (2009). The protection of selenium on ROS mediated-apoptosis by mitochondria dysfunction in cadmium-induced LLCPK1 cells. Toxicol In Vitro, 23, 288-94. https://doi.org/10.1016/j.tiv.2008.12.009
  26. Zhang Y, Luo M, Zu Y, et al (2012). Dryofragin, a phloroglucinol derivative, induces apoptosis in human breast cancer MCF-7 cells through ROS-mediated mitochondrial pathway. Chem Biol Interact, 199, 129-36. https://doi.org/10.1016/j.cbi.2012.06.007