Asian Pacific Journal of Cancer Prevention

  • 제16권10호
  • /
  • Pages.4311-4316
  • /
  • 2015
  • /
  • 1513-7368(pISSN)
  • /
  • 2476-762X(eISSN)
아시아태평양암예방학회 (Asian Pacific Journal of Cancer Prevention)
권호 표지
DOI QR코드

DOI QR Code

Dentatin from Clausena excavata Induces Apoptosis in HepG2 Cells via Mitochondrial Mediated Signaling

  • Andas, A Reenaa Joys (UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia) ;
  • Abdul, Ahmad Bustamam (UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia) ;
  • Rahman, Heshu Sulaiman (UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia) ;
  • Sukari, Mohd Aspollah (Department of Chemistry, Faculty of Science, Universiti Putra Malaysia) ;
  • Abdelwahab, Siddig Ibrahim (Medical Research Center, Faculty of Medicine, Jazan University) ;
  • Samad, Nozlena Abdul (UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia) ;
  • Anasamy, Theebaa (UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia) ;
  • Arbab, Ismail Adam (UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia)
  • 발행 : 2015.06.03
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Hepatocellular carcinoma (HCC) is a primary liver cancer with high global incidence and mortality rates. Current candidate drugs to treat HCC remain lacking and those in use possess undesirable side effects. In this investigation, the antiproliferative effects of dentatin (DTN), a natural coumarin, were evaluated on HepG2 cells and DTN's probable preliminary molecular mechanisms in apoptosis induction were further investigated. DTN significantly (p<0.05) suppressed proliferation of HepG2 cells with an $IC_{50}$ value of $12.0{\mu}g/mL$, without affecting human normal liver cells, WRL-68 ($IC_{50}$ > $50{\mu}g/mL$) causing $G_0/G_1$ cell cycle arrest via apoptosis induction. Caspase colorimetric assays showed markedly increased levels of caspase-3 and caspase-9 activities throughout the treatment period. Western blotting of treated HepG2 cells revealed inhibition of $NF-{\kappa}B$ that triggers the mitochondrial-mediated apoptotic signaling pathway by up-regulating cytoplasmic cytochrome c and Bax, and down-regulating Bcl-2 and Bcl-xL. The current findings suggest DTN has the potential to be developed further as an anticancer compound targeting human HCC.

키워드

참고문헌

  1. Abou-Jawde R, Choueiri T, Alemany C, et al (2003). An overview of targeted treatments in cancer. Clin Therap, 25, 2121-37. https://doi.org/10.1016/S0149-2918(03)80209-6
  2. Arbab IA, Abdul AB, Sukari MA, et al (2013). Dentatin isolated from Clausena excavata induces apoptosis in MCF-7 cells through the intrinsic pathway with involvement of NF-${\kappa}B$ signalling and G0/G1 cell cycle arrest: A bioassay-guided approach. J Ethnopharmacol, 145, 343-54. https://doi.org/10.1016/j.jep.2012.11.020
  3. Arbab IA, Looi CY, Abdul AB, et al (2012). Dentatin induces apoptosis in prostate cancer cells via Bcl-2, Bcl-xL, Survivin downregulation, caspase-9,-3/7 activation, and NF-${\kappa}B$ inhibition. Evid Based Complement Alternat Med, [Epub ahed of print].
  4. Brentnall M, Rodriguez-Menocal L, De Guevara RL, et al (2013). Caspase-9, caspase-3 and caspase-7 have distinct roles during intrinsic apoptosis. BMC Cell Biology, 14, 32. https://doi.org/10.1186/1471-2121-14-32
  5. Crompton M (1999). The mitochondrial permeability transition pore and its role in cell death. Biochem J, 341, 233-49. https://doi.org/10.1042/bj3410233
  6. Czabotar PE, Lessene G, Strasser A, et al (2014). Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy. Nature Rev Mol Cell Biol, 15, 49-63. https://doi.org/10.1038/nrm3722
  7. De Almagro M, Vucic D (2012). The inhibitor of apoptosis (IAP) proteins are critical regulators of signaling pathways and targets for anti-cancer therapy. Exp Oncol, 34, 200-11.
  8. Dolcet X, Llobet D, Pallares J, et al (2005). NF-$\kappa$B in development and progression of human cancer. Virchows Arch, 446, 475-82. https://doi.org/10.1007/s00428-005-1264-9
  9. Estaquier J, Vallette F, Vayssiere J-L, et al (2012). The mitochondrial pathways of apoptosis. In 'Advances in mitochondrial medicine', Eds Springer, 157-83.
  10. Ferlay J, Shin H, Bray F, et al (2013). GLOBOCAN 2008 v2. 0, cancer incidence and mortality worldwide: IARC CancerBase No. 10 [Internet]. Lyon: international agency for research on cancer
  11. Foglieni C, Meoni C, Davalli AM (2001). Fluorescent dyes for cell viability: an application on prefixed conditions. Histochem Cell Biol, 115, 223-9.
  12. Kim H, Hawke N, Baldwin A (2006). NF-${\kappa}B$ and IKK as therapeutic targets in cancer. Cell Death Different, 13, 738-47. https://doi.org/10.1038/sj.cdd.4401877
  13. Kumar R, Saha A, Saha D (2012). A new antifungal coumarin from Clausena excavata. Fitoterapia, 83, 230-3. https://doi.org/10.1016/j.fitote.2011.11.003
  14. Logue S, Martin S (2008). Caspase activation cascades in apoptosis. Biochem Soc Transact, 36, 1-9. https://doi.org/10.1042/BST0360001
  15. Mohan DS (2012). Clausena excavata Burm. f.(Rutaceae): A review of its traditional uses, pharmacological and phytochemical properties. J Med Plants Res, [Epub ahed of print].
  16. Narita M, Shimizu S, Ito T, et al (1998). Bax interacts with the permeability transition pore to induce permeability transition and cytochrome c release in isolated mitochondria. Proceed Nat Acad Sci, 95, 14681-6. https://doi.org/10.1073/pnas.95.25.14681
  17. Niles AL, Moravec RA, Riss TL (2008). Update on in vitro cytotoxicity assays for drug development. Expert Opin Drug Discov, 3, 655-69. https://doi.org/10.1517/17460441.3.6.655
  18. Ouyang L, Shi Z, Zhao S, et al (2012). Programmed cell death pathways in cancer: a review of apoptosis, autophagy and programmed necrosis. Cell proliferation, 45, 487-98. https://doi.org/10.1111/j.1365-2184.2012.00845.x
  19. Pucci B, Kasten M, Giordano A (2000). Cell cycle and apoptosis. Neoplasia, 2, 291-9. https://doi.org/10.1038/sj.neo.7900101
  20. Shamas-Din A, Kale J, Leber B, et al (2013). Mechanisms of action of Bcl-2 family proteins. Cold Spring Harb Perspect Biol, 5, 008714. https://doi.org/10.1101/cshperspect.a008714
  21. Sharif NM, Mustahil N, Noor NM, et al (2013). Cytotoxic constituents of Clausena excavata. African J Biotech, 10, 16337-41.
  22. Sultana S, Asif HM, Nazar H, et al (2014). Medicinal plants combating against cancer-a green anticancer approach. Asian Pac J Cancer Prev, 15, 4385-94. https://doi.org/10.7314/APJCP.2014.15.11.4385
  23. Sunthitikawinsakul A, Kongkathip N, Kongkathip B, et al (2003). Coumarins and carbazoles from Clausena excavata exhibited antimycobacterial and antifungal activities. Planta Medica, 69, 155-7. https://doi.org/10.1055/s-2003-37716
  24. Taufiq-Yap Y, Peh T, Ee G, et al (2007). A new cytotoxic carbazole alkaloid from Clausena excavata. Natural Product Res, 21, 810-3. https://doi.org/10.1080/14786410701258875
  25. Van Engeland M, Nieland LJ, Ramaekers FC, et al (1998). Annexin V-affinity assay: a review on an apoptosis detection system based on phosphatidylserine exposure. Cytometry, 31, 1-9. https://doi.org/10.1002/(SICI)1097-0320(19980101)31:1<1::AID-CYTO1>3.0.CO;2-R
  26. Van Engeland M, Ramaekers FC, Schutte B, et al (1996). A novel assay to measure loss of plasma membrane asymmetry during apoptosis of adherent cells in culture. Cytometry, 24, 131-9. https://doi.org/10.1002/(SICI)1097-0320(19960601)24:2<131::AID-CYTO5>3.0.CO;2-M
  27. Vermes I, Haanen C, Steffens-Nakken H, et al (1995). A novel assay for apoptosis flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled annexin V. J Immunol Methods, 184, 39-51. https://doi.org/10.1016/0022-1759(95)00072-I
  28. Volkmann N, Marassi F, Newmeyer D, et al (2014). The rheostat in the membrane: BCL-2 family proteins and apoptosis. Cell Death Different, 21, 206-15. https://doi.org/10.1038/cdd.2013.153
  29. White J (2013). Apoptosis: the intrinsic pathway. Mol Oncol, 367.
  30. Wu T-S, Furukawa H (1982). Biological and phytochemical investigation of Clausena excavata. J Natural Products, 45, 718-20. https://doi.org/10.1021/np50024a013
  31. Wu T-S, Huang S-C, Wu P-L, et al (1996). Carbazole alkaloids from Clausena excavata and their biological activity. Phytochemistry, 43, 133-40. https://doi.org/10.1016/0031-9422(96)00212-9
  32. Wurstle ML, Laussmann MA, Rehm M (2012). The central role of initiator caspase-9 in apoptosis signal transduction and the regulation of its activation and activity on the apoptosome. Experimental Cell Res, 318, 1213-20. https://doi.org/10.1016/j.yexcr.2012.02.013
  33. Xin Z-Q, Lu J-J, Ke C-Q, et al (2008). Constituents from Clausena excavata. Chem Pharmaceut Bull, 56, 827-30. https://doi.org/10.1248/cpb.56.827
  34. Zhang S-F, Wang X-L, Yang X-Q, et al (2014). Autophagy associated targeting pathways of natural products during cancer treatment. Asian Pac J Cancer Prev, 15, 10557-63.

피인용 문헌

  1. Inducing G2/M Cell Cycle Arrest and Apoptosis through Generation Reactive Oxygen Species (ROS)-Mediated Mitochondria Pathway in HT-29 Cells by Dentatin (DEN) and Dentatin Incorporated in Hydroxypropyl-β-Cyclodextrin (DEN-HPβCD) vol.17, pp.10, 2016, https://doi.org/10.3390/ijms17101653
  2. Macrophage migration inhibitory factor regulates mitochondrial dynamics and cell growth of human cancer cell lines through CD74–NF-κB signaling vol.293, pp.51, 2018, https://doi.org/10.1074/jbc.RA118.003935