DOI QR코드

DOI QR Code

Curcumin Induces Caspase Mediated Apoptosis in JURKAT Cells by Disrupting the Redox Balance

  • Gopal, Priya Kalyan ;
  • Paul, Mausumi ;
  • Paul, Santanu
  • Published : 2014.01.15

Abstract

Background: Curcumin has has been reported to exert anti-inflammatory, anti-oxidation and anti-angiogenic activity in various types of cancer. It has also been shown to induce apoptosis in leukemia cells. We aimed to unravel the role of the redox pathway in Curcumin mediated apoptosis with a panel of human leukemic cells. Materials and Methods: In this study in vitro cytotoxicity of Curcumin was measured by MTT assay and apoptotic effects were assessed by annexin V/PI, DAPI staining, cell cycle analysis, measurement of caspase activity and PARP cleavage. Effects of Curcumin on intracellular redox balance were assessed using fluorescent probes like $H_2DCFDA$, JC1 and an ApoGSH Glutathione Detection Kit respectively. Results: Curcumin showed differential anti-proliferative and apoptotic effects on different human leukemic cell lines in contrast to minimal effects on normal cells. Curcumin induced apoptosis was associated with the generation of intracellular ROS, loss of mitochondrial membrane potential, intracellular GSH depletion, caspase activation. Conclusions: As Curcumin induces programmed cell death specifically in leukemic cells it holds a great promise as a future therapeutic agent in the treatment of leukemia.

Keywords

Leukemia;ROS;GSH;mitochondrial membrane motential;cell cycle

References

  1. Huang MT, Lou YR, Ma W, et al (1994).Inhibitory effects of dietary Curcumin on fore-stomach, duodenal, and colon carcinogenesis in mice. Cancer Res, 54, 5841-7.
  2. Ghibelli L, Fanelli C, Rotilio G, et al (1998). Rescue of cells from apoptosis by inhibition of active GSH extrusion. FASEB J, 12, 479-86.
  3. Guha P, Dey A, Sen R, et al (2011). Intracellular GSH depletion triggered mitochondrial Bax translocation to accomplish resveratrol-induced apoptosis in the U937 cell line. J Pharmacol Expt Ther, 336 206-214. https://doi.org/10.1124/jpet.110.171983
  4. Huang HC, Jan TR, Yeh SF (1992). Inhibitory effect of Curcumin, an anti-inflammatory agent, on vascular smooth muscle cell proliferation. Eur J Pharmcol, 221, 381-4. https://doi.org/10.1016/0014-2999(92)90727-L
  5. Hammond CL, Madejczyk MS, Ballatori N (2004). Activation of plasma membrane reduced glutathione transport in death receptor apoptosis of HepG2 cells. Toxicol App Pharmacol, 195, 12-22. https://doi.org/10.1016/j.taap.2003.10.008
  6. He YY, Huang JL, Ramirez DC, et al (2003). Role of reduced glutathione efflux in apoptosis of immortalized human keratinocytes induced by UVA. J Biol Chem, 278, 8058-64. https://doi.org/10.1074/jbc.M207781200
  7. James JS (1996). Curcumin: clinical trial finds no antiviral effect. AIDS Treat News, 242, 1-2.
  8. Kiuchi F, Goto Y, Sugimoto N (1993).Nematocidal activity of turmeric: synergistic action of Curcuminoids. Chem Pharmacol Bul, 41, 1640-3. https://doi.org/10.1248/cpb.41.1640
  9. Kizhakkayil J, Thayyullathil F, Chathoth S, et al (2012). Glutathione regulates caspase-dependent ceramide production and Curcumin induced apoptosis in human leukemic cells. Free Rad Biol Med, 52, 1854-64. https://doi.org/10.1016/j.freeradbiomed.2012.02.026
  10. Manna A, Saha P, Sarkar A, et al (2012).Malabaricone-A induces a redox imbalance that mediates apoptosis in U937 cell line. PLoS One, 7, 1-11.
  11. Franco R, Panayiotidis MI, Cidlowski JA (2007). Glutathione depletion is necessary for apoptosis in lymphoid cells independent of reactive oxygen species formation. J Biol Chem, 282, 30452-65. https://doi.org/10.1074/jbc.M703091200
  12. Gupta SC, Patchva S, Aggarwal BB (2012). Therapeutic roles of Curcumin: lessons learned from clinical trials. Am Ass Pharm Sc, 15, 195-218.
  13. Goel A, Jhurani S, Aggarwal BB (2008). Multi-targeted therapy by Curcumin: how spicy is it? Mol Nut Food Res, 52, 1010-30. https://doi.org/10.1002/mnfr.200700354
  14. Tan TW, Tsai HR, Lu HF, et al (2006). Curcumin-induced cell cycle arrest and apoptosis in human acute promyelocyticleukemia HL-60 cells via MMP changes and caspase-3 activation. Anticancer Res, 26, 4361-71.
  15. Venkatesan N, Chandrakasan G (1995). Modulation of cyclophosphamide-induced early lung injury by Curcumin, an anti-inflammatory antioxidant. Mol Cell Biochem, 142, 79-87. https://doi.org/10.1007/BF00928916
  16. Van den, Dobbelsteen DJ, Nobel CS, et al (1996).Rapid and specific efflux of reduced glutathione during apoptosis induced by anti-Fas/APO-1 antibody. J Biol Chem, 271, 15420-7. https://doi.org/10.1074/jbc.271.26.15420
  17. Woo JH, Kim YH, Choi YJ, et al (2003). Molecular mechanisms of Curcumin-induced cytotoxicity: induction of apoptosis through generation of reactive oxygen species, down regulation of Bcl XL and IAP, the release of cytochrome c and inhibition of Akt. Carcinogenesis, 24, 1199-208. https://doi.org/10.1093/carcin/bgg082
  18. Zou H, Yang R, Hao J, et al (2003).Regulation of the Apaf-1/ caspase-9 apoptosome by caspase-3 and XIAP. J Biol Chem, 278, 8091-8. https://doi.org/10.1074/jbc.M204783200
  19. Zhou H, Beevers SC, Huang S (2011).Targets of Curcumin. Curr Drug Targets, 12, 332-47. https://doi.org/10.2174/138945011794815356
  20. Finkel T (1998). Oxygen radicals and signaling. Cur Opinion Cell Biol, 10, 248-53. https://doi.org/10.1016/S0955-0674(98)80147-6
  21. Damle RN, Temburni S, Banapour T, et al (2012). T-cell independent, B-cell receptor-mediated induction of telomerase activity differs among IGHV mutation-based subgroups of chronic lymphocytic leukemia patients. Blood, 120, 2438-49. https://doi.org/10.1182/blood-2012-02-409110
  22. Droge W (2002). Free radicals in the physiological control of cell function. Physiol Rev, 82, 47-95.
  23. Doering M, Ba LA, Lilienthal N, et al (2010). Synthesis and selective anticancer activity of organochalcogen based redox catalysts. J Med Chem, 53, 6954-63. https://doi.org/10.1021/jm100576z
  24. Finkel TR (2000). Redox-dependent signal transduction. FEBS Lett, 476, 52-4. https://doi.org/10.1016/S0014-5793(00)01669-0
  25. Franco R, Cidlowski JA (2006). SLCO/OATP-like transport of glutathione in FasLinduced apoptosis: glutathione efflux is coupled to an organic anion exchange and is necessary for the progression of the execution phase of apoptosis. J Biol Chem, 281, 29542-57. https://doi.org/10.1074/jbc.M602500200
  26. Reuter S, Eifes S, Dicato M, et al (2008). Modulation of anti apoptotic and survival pathways by Curcumin as a strategy to induce apoptosis in cancer cells. Biochem Pharmacol, 76, 1340-51. https://doi.org/10.1016/j.bcp.2008.07.031
  27. Ray PD, Huang BW, Tsuji Y (2012). Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal, 24, 981-90. https://doi.org/10.1016/j.cellsig.2012.01.008
  28. Sanchez CA, Rodriguez E, Varela E, et al (2008). Stat induced inhibition of MCF-7 breast cancer cell proliferation is related to cell cycle arrest and apoptotic and necrotic cell death mediated by an enhanced oxidative stress. Cancer Invest, 26, 698-707. https://doi.org/10.1080/07357900701874658
  29. Storz P (2005). Reactive oxygen species in tumor progression. Front Biosc, 10, 1881-96. https://doi.org/10.2741/1667
  30. Ramachandran C, Rodriguez S, Ramachandran R (2005). Expression profiles of apoptotic genes induced by Curcumin in human breast cancer and mammary epithelial cell lines. Anti Cancer Res, 25, 3293-302.
  31. Piwocka K, Bielak-Mijewska A, Sikora E (2002). Curcumin induces caspase-3independent apoptosis in human multidrugresistant cells. Ann New York Aca Sci, 973, 250-4. https://doi.org/10.1111/j.1749-6632.2002.tb04643.x
  32. Pal S, Ghosh S, Bandyopadhyay S, et al (2004). Differential expression of 9-O-acetylated sialoglycoconjugates on leukemic blasts: a potential tool for long-term monitoring of children with acute lymphoblastic leukaemia. Int J Cancer, 11, 270-7.
  33. Pelicano H, Carney D, Huang P (2004). ROS stress in cancer cells and therapeutic implications. Drug Resis Update, 7, 97-110. https://doi.org/10.1016/j.drup.2004.01.004
  34. Aggarwal BB, Kumar A, Aggarwal MS, et al (2005). Curcumin derived from turmeric (Curcuma longa): a spice for all seasons. Phytopharm Cancer Chemo Prev, 349-387.
  35. Aggarwal BB, Sundaram C, Malani N, Ichikawa H (2007). Curcumin: the Indian solid gold. AdvExpt Med Biol, 595, 1-75. https://doi.org/10.1007/978-0-387-46401-5_1
  36. Aggarwal BB, Harikumar KB (2009). Potential therapeutic effects of Curcumin, the anti inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol, 41, 40-59. https://doi.org/10.1016/j.biocel.2008.06.010
  37. Armstrong JS, Jones DP (2002). Glutathione depletion enforces the mitochondrial permeability transition and causes cell death in Bcl-2 overexpressing HL60 cells. FASEB J, 16, 1263-5.
  38. Cadenas E (2004). Mitochondrial free radical production and cell signaling. MolAspects Med, 25, 17-26. https://doi.org/10.1016/j.mam.2004.02.005

Cited by

  1. Curcumin Induces Apoptosis in SGC-7901 Gastric Adenocarcinoma Cells via Regulation of Mitochondrial Signaling Pathways vol.15, pp.9, 2014, https://doi.org/10.7314/APJCP.2014.15.9.3987
  2. Hepatoprotective Effects of Curcumin Against Diethyl Nitrosamine Induced Hepatotoxicity in Albino Rats vol.16, pp.1, 2015, https://doi.org/10.7314/APJCP.2015.16.1.103
  3. Curcumin induces the apoptosis of A549 cells via oxidative stress and MAPK signaling pathways vol.36, pp.4, 2015, https://doi.org/10.3892/ijmm.2015.2327
  4. Curcumin induces apoptosis and suppresses invasion through MAPK and MMP signaling in human monocytic leukemia SHI-1 cells pp.1744-5116, 2015, https://doi.org/10.3109/13880209.2015.1060508
  5. Synthesis and antiproliferative studies of curcumin pyrazole derivatives vol.25, pp.9, 2016, https://doi.org/10.1007/s00044-016-1628-5
  6. Cyanobacteria assisted biosynthesis of silver nanoparticles—a potential antileukemic agent vol.28, pp.6, 2016, https://doi.org/10.1007/s10811-016-0852-1
  7. Gold (III) bioreduction by cyanobacteria with special reference to in vitro biosafety assay of gold nanoparticles vol.28, pp.6, 2016, https://doi.org/10.1007/s10811-016-0880-x
  8. Curcumin Induced Human Gastric Cancer BGC-823 Cells Apoptosis by ROS-Mediated ASK1-MKK4-JNK Stress Signaling Pathway vol.15, pp.9, 2014, https://doi.org/10.3390/ijms150915754
  9. Phytochemical Modulators of Mitochondria: The Search for Chemopreventive Agents and Supportive Therapeutics vol.7, pp.9, 2014, https://doi.org/10.3390/ph7090913
  10. Treatment with a selenium-platinum compound induced T-cell acute lymphoblastic leukemia/lymphoma cells apoptosis through the mitochondrial signaling pathway vol.13, pp.3, 2017, https://doi.org/10.3892/ol.2017.5666
  11. Self-degradable curcumin polymer with anti-cancer activity pp.00218995, 2018, https://doi.org/10.1002/app.46867
  12. Molecular Targets of Curcumin and Future Therapeutic Role in Leukemia vol.06, pp.04, 2018, https://doi.org/10.4236/jbm.2018.64003
  13. Cellular and molecular mechanisms of curcumin in prevention and treatment of disease pp.1549-7852, 2019, https://doi.org/10.1080/10408398.2018.1552244
  14. Curcumin and Gastric Cancer: a Review on Mechanisms of Action pp.1941-6636, 2019, https://doi.org/10.1007/s12029-018-00186-6
  15. Extrinsic or Intrinsic Apoptosis by Curcumin and Light: Still a Mystery vol.20, pp.4, 2019, https://doi.org/10.3390/ijms20040905