Asian Pacific Journal of Cancer Prevention

  • 제15권23호
  • /
  • Pages.10495-10500
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  • 2015
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  • 1513-7368(pISSN)
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  • 2476-762X(eISSN)
아시아태평양암예방학회 (Asian Pacific Journal of Cancer Prevention)
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Bufalin Induces Mitochondrial Pathway-Mediated Apoptosis in Lung Adenocarcinoma Cells

  • Ding, Da-Wei (The First Clinical Medical College, Nanjing University of Chinese Medicine) ;
  • Zhang, Yong-Hong (The First Clinical Medical College, Nanjing University of Chinese Medicine) ;
  • Huang, Xin-En (Department of Medical Oncotherapy, Jiangsu Cancer Hospital) ;
  • An, Qing (Department of Intergrated Chinese and Western Medicine, Jiangsu Cancer Hospital) ;
  • Zhang, Xun (Department of Oncology, Jiangsu Province Hospital on Intergration of Chinese and Western Medicine)
  • 발행 : 2015.01.06
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초록

Background: To evaluate the effects of bufalin in A549 human lung adenocarcinoma epithelial cells in vitro and assess the underlying mechanisms. Materials and Methods: Human A549 non-small cell lung cancer (NSCLC) cells were treated with various concentrations of bufalin. Cell proliferation was measured by CCK-8 assay, apoptotic cell percentage was calculated by flow cytometry and morphological change was observed by inverted phase contrast microscopy/transmission electron microscopy. In addition, the membrane potential of mitochondria was detected by JC-1 fluorescence microscopy assay, and the related protein expression of cytochrome C and caspase-3 was analyzed by Western blotting. Results: Bufalin could inhibit the proliferation of A549 cells via induction of apoptosis, with the evidence of characteristic morphological changes in the nucleus and mitochondria. Furthermore, bufalin decreased the mitochondrial membrane potential with up-regulation of cytochrome C in the cytosol, and activation of caspase-3. Conclusions: Bufalin inhibits the proliferation of A549 cells and triggers mitochondria-dependent apoptosis, pointing to therapeutic application for NSCLC.

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참고문헌

  1. Banjerdpongchai R, Kongtawelert P (2011). Ethanolic extract of fermented thunb induces human leukemic HL-60 and Molt-4 cell apoptosis via oxidative stress and a mitochondrial pathway. Asian Pac J Cancer Prev, 12, 2871-4.
  2. Chen A, Yu J, Zhang L, et al (2009). Microarray and biochemical analysis of bufalin-induced apoptosis of HL-60 cells. Biotechnol Lett, 31, 487-94. https://doi.org/10.1007/s10529-008-9888-x
  3. Fogg VC, Lanning NJ, Mackeigan JP (2011). Mitochondria in cancer: at the crossroads of life and death. Chin J Cancer, 30, 526-39. https://doi.org/10.5732/cjc.011.10018
  4. Garrido C, Galluzzi L, Brunet M, et al (2006). Mechanisms of cytochrome c release from mitochondria. Cell Death Differ, 13, 1423-33. https://doi.org/10.1038/sj.cdd.4401950
  5. Igney FH, Krammer PH (2002). Death and anti-death: tumour resistance to apoptosis. Nat Rev Cancer, 2, 277-88. https://doi.org/10.1038/nrc776
  6. 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
  7. Jiang YT, Zhang Y, Luan JL, et al (2010). Effects of bufalin on the proliferation of human lung cancer cells and its molecular mechanisms of action. Cytotechnology, 62, 573-83. https://doi.org/10.1007/s10616-010-9310-0
  8. Khan KH, Montserrat BC, Molife LR (2014). Cancer therapeutics: Targeting the apoptotic pathway. Crit Rev Oncol Hematol, 90, 200-19. https://doi.org/10.1016/j.critrevonc.2013.12.012
  9. Kothakota S, Azuma T, Reinhard C, et al (1997). Caspase-3 generated fragment of gelsolin: effector of morphological change in apoptosis. Science, 278, 294-8. https://doi.org/10.1126/science.278.5336.294
  10. Krenn L, Kopp B (1998). Bufadienolides from animal and plant sources. Phytochemistry, 48, 1-29. https://doi.org/10.1016/S0031-9422(97)00426-3
  11. Kulikov AV, Shilov ES, Mufazalov IA, et al (2012). Cytochrome c: the Achilles' heel in apoptosis. Cell Mol Life Sci, 69, 1787-97. https://doi.org/10.1007/s00018-011-0895-z
  12. Li D, Qu X, Hou K, et al (2009). PI3K/Akt is involved in bufalin-induced apoptosis in gastric cancer cells. Anticancer Drugs, 20, 59-64. https://doi.org/10.1097/CAD.0b013e3283160fd6
  13. Qi FH, Inagaki Y, Gao B, et al (2011). Bufalin and cinobufagin induce apoptosis of human hepatocellular carcinoma cells via Fas- and mitochondria-mediated pathways. Cancer Sci, 102, 951-8. https://doi.org/10.1111/j.1349-7006.2011.01900.x
  14. Stinchcombe TE, Socinski MA (2009). Current treatments for advanced stage non-small cell lung cancer. Proc Am Thorac Soc, 6, 233-41. https://doi.org/10.1513/pats.200809-110LC
  15. Takai N, Kira N, Ishii T, et al (2012). Bufalin, a traditional oriental medicine, induces apoptosis in human cancer cells. Asian Pac J Cancer Prev, 13, 399-402. https://doi.org/10.7314/APJCP.2012.13.1.399
  16. Takai N, Ueda T, Nishida M, et al (2008). Bufalin induces growth inhibition, cell cycle arrest and apoptosis in human endometrial and ovarian cancer cells. Int J Mol Med, 21, 637-43.
  17. Ulivieri C (2010). Cell death: Insights into the ultrastructure of mitochondria. Tissue Cell, 42, 339-47. https://doi.org/10.1016/j.tice.2010.10.004
  18. Xie CM, Chan WY, Yu S, et al (2011). Bufalin induces autophagy-mediated cell death in human colon cancer cells through reactive oxygen species generation and JNK activation. Free Radic Biol Med, 51, 1365-75. https://doi.org/10.1016/j.freeradbiomed.2011.06.016
  19. Xue X, Yu JL, Sun DQ, et al (2014). Curcumin induces apoptosis in SGC-7901 gastric adenocarcinoma cells via regulation of mitochondrial signaling pathways. Asian Pac J Cancer Prev, 15, 3987-92. https://doi.org/10.7314/APJCP.2014.15.9.3987
  20. Yin PH, Liu X, Qiu YY, et al (2012). Anti-tumor activity and apoptosis-regulation mechanisms of bufalin in various cancers: new hope for cancer patients. Asian Pac J Cancer Prev, 13, 5339-43. https://doi.org/10.7314/APJCP.2012.13.11.5339
  21. Zou X, Liu SL, Zhou JY, et al (2012). Beta-asarone induces LoVo colon cancer cell apoptosis by up-regulation of caspases through a mitochondrial pathway in vitro and in vivo. Asian Pac J Cancer Prev, 13, 5291-8. https://doi.org/10.7314/APJCP.2012.13.10.5291

피인용 문헌

  1. Bufalin Induces Mitochondria-Dependent Apoptosis in Pancreatic and Oral Cancer Cells by Downregulating hTERT Expression via Activation of the JNK/p38 Pathway vol.2015, pp.1741-4288, 2015, https://doi.org/10.1155/2015/546210