Asian Pacific Journal of Cancer Prevention

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

DOI QR Code

Radix Tetrastigma Hemsleyani Flavone Induces Apoptosis in Human Lung Carcinoma A549 Cells by Modulating the MAPK Pathway

  • Zhong, Liang-Rui (TongDe Hospital of ZheJiang Province, Affiliated Hospital of Zhejiang Chinese Medical University) ;
  • Chen, Xian (ZheJiang HuaYi Pharmaceutical Co. Ltd.) ;
  • Wei, Ke-Min (Zhejiang Academy of Traditional Chinese Medicine)
  • Published : 2013.10.30
Download PDF
⟨ Previous Next ⟩

Abstract

Radix Tetrastigma Hemsleyani Flavone (RTHF) is widely used as a traditional herb for its detoxification and anti-inflammation activity. Recently, several studies have shown that RTHF can inhibit growth and induce apoptosis in human cancer cell lines. However, the mechanisms are not completely understood yet. In this study we investigated the potential effects of RTHF on growth and apoptosis in human lung adenocarcinoma A549 cells as well as its mechanisms. A549 cells were treated with RTHF at various concentrations for different times. In vitro the MTT assay showed that RTHF had obvious anti-proliferation effects on A549 cells in a dose- and time-dependent manner. Cell morphological changes observed by inverted microscope and Hoechst33258 methods were compared with apoptotic changes observed by fluorescence microscope. Cell apoptosis inspected by flow cytometry showed significant increase in the treatment group over the control group (P<0.01). Expression of apoptosis related Bax/Bcl-2, caspases and MAPK pathway proteins were detected by Western blotting. The results showed that RTHF up-regulated the Bax/Bcl-2 ratio and cle-caspase3/9, cle-PARP expression in a dose-dependent manner. Expression of p-p38 increased, p-ERK decreased significantly and that of p-JNK was little changed in the RTHF group when compared with the control group. These results suggest that RTHF might exert anti-growth and apoptosis activity against lung cancer A549 cells through activation of caspases and Bcl-2 family proteins and the MAPK pathway, therefore presenting as a promising therapeutic agent for the treatment of lung cancer.

Keywords

References

  1. De Luca V, Salim V, Atsumi SM, et al (2012). Mining the biodiversity of plants: a revolution in the making. Science, 336, 1658-61. https://doi.org/10.1126/science.1217410
  2. De Petris L, Crino L, Scagliotti GV, et al (2006). Treatment of advanced non-small cell lung cancer. Ann Oncol, 2, 1136-41.
  3. Denault JB, Boatright K (2004). Apoptosis in Biochemistry and Structural Biology. 3-8 February 2004, Keystone, CO, USA. IDrugs, 7, 315-17.
  4. Ding GQ, Zheng JX, Wei KM, e al (2005). Toxicological Effects of the Extract of Tetrastigma hemsleyanum Diels et. Gflg on Hepatocellular Carcinoma Cell Line HepG2 and Primary Rat Hepatocytes in vitro. J Zhejiang Prev Med, 17, 1-5.
  5. Emi M, Kim R, Tanabe K, et al (2005). Targeted therapy against Bcl-2-related proteins in breast cancer cells. Breast Cancer Res, 7, R940-52. https://doi.org/10.1186/bcr1323
  6. Feng ZQ, Ni KF, He Y, et al (2006). Experimental study on effect of Tetrastigma hemsleyanum Diels et Gilg flavone on inducing apoptosis of SGC-7901 cell line in vitro. Chin J Clin Pharmacol Ther, 11, 669-72.
  7. Gupta S, Afaq F, Mukhtar H (2002). Involvement of nuclear factor-kappa B, Bax and Bcl-2 in induction of cell cycle arrest and apoptosis by apigenin in human prostate carcinoma cells. Oncogene, 21, 3727-38. https://doi.org/10.1038/sj.onc.1205474
  8. Heimlich G, McKinnon AD, Bernardo K, et al (2004). Bax-induced cytochrome c release from mitochondria depend sonalpha-helices-5 and-6. Biochem J, 378, 247-55. https://doi.org/10.1042/BJ20031152
  9. Hengartner MO (2000). The biochemistry of apoptosis. Nature, 407, 770-6. https://doi.org/10.1038/35037710
  10. Johnson GL, Lapadat R (2002). Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science, 298, 1911-12. https://doi.org/10.1126/science.1072682
  11. Kim YK, Kim HJ, Kwon CH, et al (2005). Role of ERK activation in cisplatin-induced apoptosis in OK renal epithelial cells. J Appl Toxicol, 25, 374-82. https://doi.org/10.1002/jat.1081
  12. Lee SH, Kim HS, Park WS, et al (2002). Non-small cell lung cancers frequently express phosphorylated Akt; an immunohistochemical study. APMIS, 110, 587-92. https://doi.org/10.1034/j.1600-0463.2002.11007811.x
  13. Li HM, Pu JB, Zheng JX, et al (2012). The inhibition effect of Radix Tetrastigma Hemsleyani extract on Lewis lung cancer in mice transplanted tumor and immune function. Chin J Med Sci Tech, 19, 229-30.
  14. Li WY, Chan SW, Guo DJ, et al (2009). Water extract of Rheum officinale Baill.induces apoptosis in human lung adenocarcinoma A549 and human breast cancer MCF-7 cell lines. J Ethnopharmacol, 124, 251-56. https://doi.org/10.1016/j.jep.2009.04.030
  15. Liu W, Li SY, Huang XE, et al (2012). Inhibition of tumor growth in vitro by a combination of extracts from Rosa roxburghii Tratt and Fagopyrum cymosum. Asian Pac J Cancer Prev, 13, 2409-14. https://doi.org/10.7314/APJCP.2012.13.5.2409
  16. Liu ZB, Hou YF, Min D, et al (2009). PA-MSHA inhibits proliferation and induces apoptosis through the up-regulation and activation of caspases in the human breast cancer cell lines. J Cell Biochem, 108, 195-206. https://doi.org/10.1002/jcb.22241
  17. Messina ME Jr, Halaby R (2011). Does triptolide induce lysosomal-mediated apoptosis in human breast cancer cells? Med Hypotheses, 77, 91-3. https://doi.org/10.1016/j.mehy.2011.03.034
  18. Mignotte B, Vayssiere JL (1998). Mitochondria and apoptosis. Eur J Biochem, 252, 1-15. https://doi.org/10.1046/j.1432-1327.1998.2520001.x
  19. Mishra BB, Tiwari VK (2011). Natural products: an evolving role in future drug discovery. Eur J Med Chem, 46, 4769-807. https://doi.org/10.1016/j.ejmech.2011.07.057
  20. Mondal S, Bandyopadhyay S, Ghosh MK, et al (2012). Natural products: promising resources for cancer drug discovery. Anticancer Agents Med Chem, 12, 49-75. https://doi.org/10.2174/187152012798764697
  21. Ni KF, Ding ZS, Huang T, et al (2008). Inhibition Effect of Tetrastigma Hemsleyanum Diels et Gilg Flavone on H-22 Solid Tumors in Mice. J Zhejiang Chin Med Uni, 32, 732-4.
  22. Pearson G, Robinson F, Gibson TB, et al (2001). Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev, 22, 153-83.
  23. Raman M, Chen W, Cobb MH (2007). Differential regulation and properties of MAPKs. Oncogene, 26, 3100-12. https://doi.org/10.1038/sj.onc.1210392
  24. Shi Y (2002). Mechanisms of caspase activation and inhibition during apoptosis. Mol Cell, 9, 459-70. https://doi.org/10.1016/S1097-2765(02)00482-3
  25. Sun SY, Hail N Jr, Lotan R (2004). Apoptosis as a novel target for cancer chemoprevention. J Nati Cancer Inst, 96, 662-72. https://doi.org/10.1093/jnci/djh123
  26. Tournier C, Hess P, Yang DD, et al (2000). Requirement of JNK for stress-induced activation of the cytochrome c-mediated death pathway. Science, 288, 870-4. https://doi.org/10.1126/science.288.5467.870
  27. Xu CJ, Wu PG, Meng J, et al (2010). Inhibitory effect on proliferation of K562 cell line by extract from tetrastigma hemsleyanum diels et. Gilg. Chin J Health Lab Tech, 20, 2801-03.
  28. Zinkel S, Gross A, Yang E (2006). BCL2 family in DNA damage and cell cycle control. Cell Death Differ, 13, 1351-9. https://doi.org/10.1038/sj.cdd.4401987

Cited by

  1. In vitro Study of Nucleostemin as a Potential Therapeutic Target in Human Breast Carcinoma SKBR-3 Cells vol.15, pp.5, 2014, https://doi.org/10.7314/APJCP.2014.15.5.2291
  2. Autophagy-associated Targeting Pathways of Natural Products during Cancer Treatment vol.15, pp.24, 2014, https://doi.org/10.7314/APJCP.2014.15.24.10557
  3. Anti-proliferation Effects of Isorhamnetin on Lung Cancer Cells in Vitro and in Vivo vol.16, pp.7, 2015, https://doi.org/10.7314/APJCP.2015.16.7.3035
  4. Diels et Gilg and Their Antioxidant Activity vol.39, pp.6, 2015, https://doi.org/10.1111/jfpp.12464
  5. Stromal interaction molecule 1 plays an important role in gastric cancer progression vol.35, pp.6, 2016, https://doi.org/10.3892/or.2016.4704
  6. Inhibition of SOCs Attenuates Acute Lung Injury Induced by Severe Acute Pancreatitis in Rats and PMVECs Injury Induced by Lipopolysaccharide pp.1573-2576, 2016, https://doi.org/10.1007/s10753-016-0335-1
  7. Protective Effects of Acupuncture in Cardiopulmonary Bypass-Induced Lung Injury in Rats vol.40, pp.4, 2017, https://doi.org/10.1007/s10753-017-0570-0
  8. The phenolic profiles of Radix Tetrastigma after solid phase extraction (SPE) and their antitumor effects and antioxidant activities in H22 tumor-bearing mice pp.2042-650X, 2017, https://doi.org/10.1039/C7FO00769H
  9. A New Polyunsaturated Lipid from Tetrastigma hemsleyanum vol.54, pp.3, 2018, https://doi.org/10.1007/s10600-018-2371-6