Asian Pacific Journal of Cancer Prevention

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

DOI QR Code

Combination of Nimbolide and TNF-α-Increases Human Colon Adenocarcinoma Cell Death through JNK-mediated DR5 Up-regulation

  • Boonyarat, Chantana (Faculty of Pharmaceutical Sciences, Khon Kaen University) ;
  • Yenjai, Chavi (Natural Products Research Unit, Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Khon Kaen University) ;
  • Reubroycharoen, Prasert (Department of Chemical Technology, Faculty of Science, Chulalongkorn University) ;
  • Waiwut, Pornthip (Faculty of Pharmaceutical Sciences, Ubon Ratchathani University)
  • Published : 2016.05.01
⟨ Previous Next ⟩

Abstract

Tumor necrosis factor ($TNF-{\alpha}$), an inflammatory cytokine that plays an important role in the control of cell proliferation, differentiation, and apoptosis, has previously been used in anti-cancer therapy. However, the therapeutic applications of $TNF-{\alpha}$ are largely limited due to its general toxicity and anti-apoptotic influence. To overcome this problem, the present study focused on the effect of active constituents isolated from a medicinal plant on $TNF-{\alpha}$-induced apoptosis in human colon adenocarcinoma (HT-29) cells. Nimbolide from Azadirachta indica was evaluated for cytotoxicity by methyl tetrazolium 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay and phase contrast microscopy. Effects on apoptotic signaling proteins were investigated using Western blot analysis. Nimbolide showed cytotoxicity against HT-29 cells that was significantly different from the control group (p<0.01), a concentration of $10{\mu}M$ significantly inducing cell death (p<0.01). In combination with $TNF-{\alpha}$, nimbolide significantly enhanced-induced cell death. In apoptotic pathway, nimbolide activated c-Jun N-terminal kinase (JNK) phosphorylation, BH3 interacting-domain death agonist (Bid) and up-regulated the death receptor 5 (DR5) level. In the combination group, nimbolide markedly sensitized $TNF-{\alpha}$-induced JNK, Bid, caspase-3 activation and the up-regulation of DR5. Our findings overall indicate that nimbolide may enhance $TNF-{\alpha}$-mediated cellular proliferation inhibition through increasing cell apoptosis of HT-29 cells by up-reglation of DR5 expression via the JNK pathway.

Keywords

Acknowledgement

Supported by : Chulalongkorn University

References

  1. Boonyarat C, Yenjai C, Vajragupta O, Waiwut P (2014). Heptaphylline induces apoptosis in human colon adenocarcinoma cells through bid and Akt/NF-${\kappa}B$ (p65) pathways. Asian Pac J Cancer Prev, 15, 10483-97.
  2. Brenner D, Blaser H, Mak TW (2015). Regulation of tumour necrosis factor signalling: live or let die. Nat Rev Immunolm, 6, 362-74.
  3. Chung TW, Tan KT, Chan HL, et al (2014). Induction of indoleamine 2,3-dioxygenase (IDO) enzymatic activity contributes to interferon-gamma induced apoptosis and death receptor 5 expression in human non-small cell lung cancer cells. Asian Pac J Cancer Prev, 15, 7995-8001. https://doi.org/10.7314/APJCP.2014.15.18.7995
  4. Clark IA (2007). How TNF was recognized as a key mechanism of disease. Cytokine Growth Factor Rev, 18, 335-343. https://doi.org/10.1016/j.cytogfr.2007.04.002
  5. Debatin KM and Krammer. PM (2004). Death receptors in chemotherapy and cancer Oncogene, 23, 2950-66. https://doi.org/10.1038/sj.onc.1207558
  6. Deng Y, Ren X, Yang L, et al (2003). A JNK-dependent pathway is required for TNFalpha-induced apoptosis. Cell, 115, 61-70. https://doi.org/10.1016/S0092-8674(03)00757-8
  7. Doss GP, Agoramoorthy G, Chakraborty C (2014). TNF/TNFR: drug target for autoimmune diseases and immune-mediated inflammatory diseases. Front Biosci, 19, 1028-40 https://doi.org/10.2741/4265
  8. Elmore S (2007). Apoptosis: a review of programmed cell death. Toxicol Pathol, 35, 495-516. https://doi.org/10.1080/01926230701320337
  9. Elumalai P, Arunakaran J (2014). Review on molecular and chemopreventive potential of nimbolide in cancer. Genomics Inform, 12, 156-64. https://doi.org/10.5808/GI.2014.12.4.156
  10. Fassl A, Tagscherer KE, Richter J et al (2015). Inhibition of Notch1 signaling overcomes resistance to the death ligand Trail by specificity protein 1-dependent upregulation of death receptor 5. Cell Death Dis, 15, 1921.
  11. Gerard I, Vousden E, Vousden KH (2001). Progress proliferation, cell cycle and apoptosis in cancer. Nature, 411, 342-8. https://doi.org/10.1038/35077213
  12. Gupta SC, Prasad S, Sethumadhavan DR, et al (2013). Nimbolide, a limonoid triterpene, inhibits growth of human colorectal cancer xenografts by suppressing the proinflammatory microenvironment. Clin Cancer Res, 19, 4465-76. https://doi.org/10.1158/1078-0432.CCR-13-0080
  13. Hanahan D, Weinberg RA (2011). Hallmarks of cancer: the next generation. Cell, 144, 646-74. https://doi.org/10.1016/j.cell.2011.02.013
  14. Jang MK, Kim HS, Chung YH (2014). Clinical aspects of tumor necrosis factor-${\alpha}$ signaling in hepatocellular carcinoma. Curr Pharm Des, 17, 2799-2808.
  15. Jang JY, Kim SJ, Cho EK et al (2014). TRAIL enhances apoptosis of human hepatocellular carcinoma cells sensitized by hepatitis C virus infection: therapeutic implications. PLoS One, 9, 98171. https://doi.org/10.1371/journal.pone.0098171
  16. Jin S, Ray RM, Johnson LR (2007). TNF-alpha/cycloheximide-induced apoptosis in intestinal epithelial cells requires Rac1-regulated reactive oxygen species. Am J Physiol Gastrointest Liver Physiol, 294, 928-37.
  17. Kalimuthu S and Kwon KS (2013). Cell survival and apoptosis signaling as therapeutic target for cancer: marine bioactive compounds. Int J Mol Sci, 14, 2334-54. https://doi.org/10.3390/ijms14022334
  18. Koff JL, Ramachandiran S, Bernal-Mizrachi L (2015). A time to kill: targeting apoptosis in cancer. Int J Mol Sci, 16, 2942-55. https://doi.org/10.3390/ijms16022942
  19. Lavrik IN (2014). Systems biology of death receptor networks: live and let die. Cell Death Dis, 5, 1259. https://doi.org/10.1038/cddis.2014.160
  20. Marques-Fernandez F, Planells-Ferrer L, Gozzelino R, et al (2013). TNF-${\alpha}$ induces survival through the FLIP-L-dependent activation of the MAPK/ERK pathway. Cell Death Dis, 14, 493.
  21. Muc M, Baranowski M (1995). Effect of intravenous treatment with tumor necrosis factor alpha in patients with advanced cancer-phase I clinical trials. Przegl Lek. 52, 496-8.
  22. Ouyang L, Shi Z, Zhao S et al (2012). Programmed cell death pathways in cancer: a review of apoptosis, autophagy and programmed necrosis. Cell Prolif, 45, 487-498. https://doi.org/10.1111/j.1365-2184.2012.00845.x
  23. Park MH, Kim JH, Chung YH, et al (2016). Bakuchiol sensitizes cancer cells to TRAIL through ROS- and JNK-mediated upregulation of death receptors and downregulation of survival proteins. Biochem Biophys Res Commun, 16, 30443-50.
  24. Patel SM, Venkata KC, Bhattacharyya P, et al (2016). Potential of neem (Azadirachta indica L.) for prevention and treatment of oncologic diseases. Semin Cancer Biol, 16, 30006-12
  25. Paul AT, Gohil VM, Bhutani KK (2006). Modulating TNF-alpha signaling with natural products. Drug Discov Today, 11, 725-32. https://doi.org/10.1016/j.drudis.2006.06.002
  26. Rochanakij S, Thebtaranonth Y, Yenjai C, Yuthavong Y (1985). Nimbolide, a constituent of Azadirachta indica, inhibits Plasmodium falciparum in culture. Southeast Asian J Trop Med Public Health, 16, 66-72.
  27. Sritanaudomchai H, Kusamran T, Kuakulkiat W, et al (2005). Quinone reductase inducers in Azadirachta indica A. Juss flowers, and their mechanisms of action. Asian Pac J Cancer Prev, 6, 263-9.
  28. Su Z, Yang Z, Xu Y, et al (2015). Apoptosis, autophagy, necroptosis, and cancer metastasis. Mol Cancer, 14, 48.
  29. Waiwut P, Shin MS, Inujima A, et al (2011). Gomisin N enhances TNF-${\alpha}$-induced apoptosis via inhibition of the NF-${\kappa}B$ and EGFR survival pathways. Mol Cell Biochem, 350, 169-175. https://doi.org/10.1007/s11010-010-0695-z
  30. Walczak H (2013). Death receptor-ligand systems in cancer, cell death, and inflammation. Cold Spring Harb Perspect Biol, 5, 8698. https://doi.org/10.1101/cshperspect.a008698
  31. Walsh LJ, Trinchieri G, Waldorf HA, Whitaker D, Murphy GF (1991) Human dermal mast cells contain and release tumor necrosis factor alpha, which induces endothelial leukocyte adhesion molecule 1. Proc Natl Acad Sci USA, 88, 4220-4. https://doi.org/10.1073/pnas.88.10.4220
  32. Wu H, Che X, Zheng Q, et al (2014). Caspases: A Molecular Switch Node in the Crosstalk between Autophagy and Apoptosis. Int J Biol Sci, 10, 1072-83. https://doi.org/10.7150/ijbs.9719

Cited by

  1. Inhibition of cell survival and proliferation by nimbolide in human androgen-independent prostate cancer (PC-3) cells: involvement of the PI3K/Akt pathway vol.427, pp.1-2, 2017, https://doi.org/10.1007/s11010-016-2898-4