Asian Pacific Journal of Cancer Prevention

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

DOI QR Code

Anticancer Effects of Thymoquinone, Caffeic Acid Phenethyl Ester and Resveratrol on A549 Non-small Cell Lung Cancer Cells Exposed to Benzo(a)pyrene

  • Ulasli, Sevinc Sarinc (Department of Pulmonary Diseases, Faculty of Medicine, Afyon Kocatepe University) ;
  • Celik, Sefa (Department of Medical Biochemistry, Faculty of Medicine, Afyon Kocatepe University) ;
  • Gunay, Ersin (Department of Pulmonary Diseases, Faculty of Medicine, Afyon Kocatepe University) ;
  • Ozdemir, Mehmet (Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Afyon Kocatepe University) ;
  • Hazman, Omer (Department of Chemistry, Faculty of Science and Arts, Afyon Kocatepe University) ;
  • Ozyurek, Arzu (Department of Chemistry, Faculty of Science and Arts, Afyon Kocatepe University) ;
  • Koyuncu, Tulay (Department of Pulmonary Diseases, Faculty of Medicine, Afyon Kocatepe University) ;
  • Unlu, Mehmet (Department of Pulmonary Diseases, Faculty of Medicine, Afyon Kocatepe University)
  • Published : 2013.10.30
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Phytochemical compounds are emerging as a new generation of anticancer agents with limited toxicity in cancer patients. The purpose of this study was to investigate the potential effcts of thymoquinone, caffeic acid phenylester (CAPE) and resveratrol on inflammatory markers, oxidative stress parameters, mRNA expression levels of proteins and survival of lung cancer cells in Vitro. Materials and Methods: The A549 cell line was treated with benzo(a)pyrene, benzo(a)pyrene plus caffeic acid phenylester (CAPE), benzo(a)pyrene plus resveratrol (RES), and benzo(a)pyrene plus thymoquinone (TQ). Inflammatory markers, oxidative stress parameters, mRNA expression levels of apoptotic and anti-apoptotic proteins and cell viability were assessed and results were compared among study groups. Results: TQ treatment up-regulated Bax and down-regulated Bcl2 proteins and increased the Bax/Bcl2 ratio. CAPE and TQ also up-regulated Bax expression. RES and TQ down-regulated the expression of Bcl-2. All three agents decreased the expression of cyclin D and increased the expression of p21. However, the most significant up-regulation of p21 expression was observed in TQ treated cells. CAPE, RES and TQ up-regulated TRAIL receptor 1 and 2 expression. RES and TQ down-regulated the expression of NF-kappa B and IKK1. Viability of CAPE, RES and TQ treated cells was found to be significantly decreased when compared with the control group (p=0.004). Conclusions: Our results revealed up-regulation of the key upstream signaling factors, which ultimately cause increase in their regulatory p53 levels affecting the induction of G2/M cell cycle arrest and apoptosis. Overall these results provide mechanistic insights for understanding the molecular basis and utility of the anti-tumor activity of TQ, RES and CAPE.

Keywords

References

  1. Attoub S, Sperandio O, Raza H, et al (2013). Thymoquinone as an anticancer agent: evidence from inhibition of cancer cells viability and invasion in vitro and tumor growth in vivo. Fundam Clin Pharmacol, 27, 557-69. https://doi.org/10.1111/j.1472-8206.2012.01056.x
  2. Bae S, Lee EM, Cha HJ, et al (2011). Resveratrol alters microRNA expression profiles in A549 human non-small cell lung cancer cells. Mol Cells, 32, 243-9. https://doi.org/10.1007/s10059-011-1037-z
  3. Binkova B, Giguere Y, Rossner P Jr, Dostal M, Sram RJ (2000). The effect of dibenzo[a,1]pyrene and benzo[a]pyrene on human diploid lung fibroblasts: the induction of DNA adducts, expression of p53 and p21 (WAF1) proteins and cell cycle distribution. Mutat Res, 471, 57-70. https://doi.org/10.1016/S1383-5718(00)00111-X
  4. Bradford MM (1976). A rapid and sensitive for the quantitation of microgram quantitites of protein utilizing the principle of protein-dye binding. Anal Biochem, 72, 248-54. https://doi.org/10.1016/0003-2697(76)90527-3
  5. Brugarolas J, Chandrasekaran C, Gordon JI, et al (1995). Radiation-induced cell cycle arrest compromised by p21 deficiency. Nature, 377, 552-7. https://doi.org/10.1038/377552a0
  6. Buetler E, Dubon O, Kelly, BM (1963). Improved method for the determination of blood glutathione. J Lab Clin Med, 61, 882-8.
  7. Chellappan SS, Giordano A, Fisher PB (1998). Role of cyclin dependent kinases and their inhibitors in cellular differentiation and development. Curr Top Microbiol Immunol, 227, 57-103.
  8. Chen J, Saha P, Kornbluth S, Dynlacht BD, Dutta A (1996). Cyclin-binding motifs are essential for the function of p21CIP1. Mol Cell Biol, 16, 4673-82.
  9. Chen MF, Wu CT, Chen YJ, Keng PC, Chen WC (2004). Cell killing and radiosensitization by caffeic acid phenethyl ester (CAPE) in lung cancer cells. J Radiat Res, 45, 253-60. https://doi.org/10.1269/jrr.45.253
  10. Chen Z, Jin K, Gao L, et al (2010). Anti-tumor effects of bakuchiol, an analogue of resveratrol, on human lung adenocarcinoma A549 cell line. Eur J Pharmacol, 643, 170-9. https://doi.org/10.1016/j.ejphar.2010.06.025
  11. Cheng EH, Wei MC, Weiler S, et al (2001). Bcl-2, Bcl-X(L) sequester BH3 domain-only molecules preventing BAX- and BAK-mediated mitochondrial apoptosis. Mol Cell, 8, 705-11. https://doi.org/10.1016/S1097-2765(01)00320-3
  12. Connelly L, Barham W, Onishko HM, et al (2011). Inhibition of NF-kappa B activity in mammary epithelium increases tumor latency and decreases tumor burden. Oncogene, 30, 1402-12. https://doi.org/10.1038/onc.2010.521
  13. Cotgreave IA, Gerdes RG (1998). Recent trends in glutathione biochemistry-glutathione-protein interactions: a molecular link between oxidative stres and cell proliferation? Biochem Biophys Res Commun, 242, 1-9. https://doi.org/10.1006/bbrc.1997.7812
  14. Devesa SS, Bray F, Vizcaino AP, Parkin DM (2005). International lung cancer trends by histologic type: male:female diff erences diminishing and adenocarcinoma rates rising. Int J Cancer, 117, 294-9. https://doi.org/10.1002/ijc.21183
  15. Eom SY, Yim DH, Moon SI, et al (2013). Polycyclic aromatic hydrocarbon-induced oxidative stress, antioxidant capacity, and the risk of lung cancer: a pilot nested case-control study. Anticancer Res, 33, 3089-97.
  16. Erel O (2004). A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem, 37, 277-85. https://doi.org/10.1016/j.clinbiochem.2003.11.015
  17. Erel O (2005). A new automated colorimetric method for measuring total oxidant status. Clin Biochem, 38, 1103-11. https://doi.org/10.1016/j.clinbiochem.2005.08.008
  18. Esen C, Alkan BA, Kirnap M, et al (2012). The effects of chronic periodontitis and rheumatoid arthritis on serum and gingival crevicular fluid total antioxidant/oxidant status and oxidative stress index. J Periodontol, 83, 773-9. https://doi.org/10.1902/jop.2011.110420
  19. Gartel AL, Tyner AL (2002). The role of the cyclin-dependent kinase inhibitor p21 in apoptosis. Mol Cancer Ther, 1, 639-49.
  20. Goldstraw P, Ball D, Jett JR, et al (2011). Non-small-cell lung cancer. Lancet, 78, 1727-40.
  21. 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
  22. Kaspin LC, Baird WM (1996). Anti-benzo[a]pyrene-7,8-diol-9,10- epoxide treatment increases levels of proteins p53 and p21WAF1 in the human mammary carcinoma cell line MCF-7. Polycyclic Arom Comp, 10, 299-306. https://doi.org/10.1080/10406639608034710
  23. Khan A, Vaibhav K, Javed H , et al (2012). Attenuation of Ab-induced neurotoxicity by thymoquinone via inhibition of mitochondrial dysfunction and oxidative stress. Mol Cell Biochem, 369, 55-65. https://doi.org/10.1007/s11010-012-1368-x
  24. Kode A, Rajendrasozhan S, Caito S, et al (2008). Resveratrol induces glutathione synthesis by activation of Nrf2 and protects against cigarette smoke-mediated oxidative stress in human lung epithelial cells. Am J Physiol Lung Cell Mol Physiol, 294, 478-88.
  25. Komiya T, Hosono Y, Hirashima T, et al (1997). p21 expression as a predictor for favorable prognosis in squamous cell carcinoma of the lung. Clin Cancer Res, 3, 1831-5.
  26. Kubota T, Uemura Y, Kobayashi M, Taguchi H (2003). Combined effects of resveratrol and paclitaxel on lung cancer cells. Anticancer Res, 23, 4039-46.
  27. Li Y, Zhang S, Geng JX, Hu XY (2013). Curcumin inhibits human non-small cell lung cancer A549 cell proliferation through regulation of Bcl-2/Bax and cytochrome C. Asian Pac J Cancer Prev, 14, 4599-602. https://doi.org/10.7314/APJCP.2013.14.8.4599
  28. Lin HP, Kuo LK, Chuu CP (2012). Combined treatment of curcumin and small molecule inhibitors suppresses proliferation of A549 and H1299 human non-small-cell lung cancer cells. Phytother Res, 26, 122-6. https://doi.org/10.1002/ptr.3523
  29. Lozano R, Naghavi M, Foreman K, et al (2012). Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet, 380, 2095-128. https://doi.org/10.1016/S0140-6736(12)61728-0
  30. Luch A, Kudla K, Seidel A, et al (1999). The level of DNA modification by (C)-syn- (11S,12R,13S,14R)- and (-)-anti-(11R,12S,13S,14R)-dihydrodiol epoxides of dibenzo[a,l] pyrene determined the effect on the proteins p53 and p21WAF1 in human mammary carcinoma cell line MCF-7. Carcinogenesis, 20, 859-65. https://doi.org/10.1093/carcin/20.5.859
  31. Malhotra A, Nair P, Dhawan DK (2011). Curcumin and resveratrol synergistically stimulate p21 and regulate cox-2 by maintaining adequate zinc levels during lung carcinogenesis. Eur J Cancer Prev, 20, 411-6. https://doi.org/10.1097/CEJ.0b013e3283481d71
  32. Miranda KM, Espey MG, Wink DA (2001). A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide, 5, 62-71. https://doi.org/10.1006/niox.2000.0319
  33. Natarajan K, Singh S, Burke TR Jr, Grunberger D, Aggarwal BB (1996). Caffeic acid phenethyl ester is a potent and specific inhibitor of activation of nuclear transcription factor NF-kappa B. Proc Natl Acad Sci USA, 93, 9090-5. https://doi.org/10.1073/pnas.93.17.9090
  34. Niklinski J, Niklinska W, Laudanski J, Chyczewska E, Chyczewski L (2001). Prognostic molecular markers in non-small cell lung carcinoma. Lung Cancer, 2, 53-8.
  35. Orsolic N, Knezevic AH, Sver L, Terzic S, Basic I (2004). Immunomodulatory and antimetastatic action of propolis and related polyphenolic compounds. J Ethnopharmacol, 94, 307-15. https://doi.org/10.1016/j.jep.2004.06.006
  36. Orsolic N, Sver L, Terzic S, Basic I (2005). Peroral application of water-soluble derivative of propolis (WSDP) and its related polyphenolic compounds and their influence on immunological and antitumour activity. Vet Res Commun, 29, 575-93. https://doi.org/10.1007/s11259-005-3303-z
  37. Pfeifer GP, Denissenko MF, Olivier M, et al (2002). Tobacco smoke carcinogens, DNA damage and p53 mutations in smoking-associated cancers. Oncogene, 21, 7435-51. https://doi.org/10.1038/sj.onc.1205803
  38. Ramet M, Castren K, Jarvinen K, et al (1995). p53 protein expression is correlated with benzo[a]pyrene-DNA adducts in carcinoma cell lines. Carcinogenesis, 16, 2117-24. https://doi.org/10.1093/carcin/16.9.2117
  39. Randhawa MA, Alghamdi MS (2011). Anticancer activity of nigella saliva (Black Seed): a review. Am J Chin Med, 39, 1075-91. https://doi.org/10.1142/S0192415X1100941X
  40. Rosell R, Bivona TG, Karachaliou N (2013). Genetics and biomarkers in personalisation of lung cancer treatment Lancet, 382, 720-31. https://doi.org/10.1016/S0140-6736(13)61715-8
  41. Sethi G, Ahn KS, Aggarwal BB (2008). Targeting nuclear factor-_B activation pathway by thymoquinone: role in suppression of antiapoptotic gene products and enhancement of apoptosis. Mol Cancer Res, 6, 1059-70. https://doi.org/10.1158/1541-7786.MCR-07-2088
  42. Shigeoka Y, Igishi T, Matsumoto S, et al (2004). Sulindac sulfide and caffeic acid phenethyl ester suppress the motility of lung adenocarcinoma cells promoted by transforming growth factor-beta through Akt inhibition. J Cancer Res Clin Oncol, 130, 146-52. https://doi.org/10.1007/s00432-003-0520-0
  43. Shoji T, Tanaka F, Takata T, et al (2002). Clinical significance of p21 expression in non-small-cell lung carcinoma. J Clin Oncol, 20, 3865-71. https://doi.org/10.1200/JCO.2002.09.147
  44. Tampioa M, Loikkanena J, Myllynenb P, Mertanena A, Vahakangasa KH (2008). Benzo(a)pyrene increases phosphorylation of p53 at serine 392 in relation to p53 induction and cell death in MCF-7 cells. Toxicol Lett, 178, 152-9. https://doi.org/10.1016/j.toxlet.2008.03.006
  45. Woo CC, Kumar AP, Sethi G, Tan KH (2012). Thymoquinone: potential cure for inflammatory disorders and cancer. Biochem Pharmacol, 83, 443-51. https://doi.org/10.1016/j.bcp.2011.09.029
  46. Yin HT, Tian QZ, Guan L, et al (2013). In vitro and in vivo evaluation of the antitumor efficiency of resveratrol against lung cancer. Asian Pac J Cancer Prev, 14, 1703-6. https://doi.org/10.7314/APJCP.2013.14.3.1703
  47. Yoshioka T, Kawada K, Shimada T, Mori M (1979). Lipid peroxidation in maternal and cord blood and protective mechanisms against activated-oxygen toxicity in the blood. Am J Obstet Gynecol, 135, 372-5.
  48. Zhang W, Wang X, Chen T (2011). Resveratrol induces mitochondria-mediated AIF and to a lesser extent caspase-9-dependent apoptosis in human lung adenocarcinoma ASTC-a-1 cells. Mol Cell Biochem, 354, 29-37. https://doi.org/10.1007/s11010-011-0802-9
  49. Zhou YT, Li K, Tian H (2013). Effects of vinorelbine on cisplatin resistance reversal in human lung cancer A549/DPP cells. Asian Pac J Cancer Prev, 14, 4635-9. https://doi.org/10.7314/APJCP.2013.14.8.4635

Cited by

  1. Matrine Reduces Proliferation of Human Lung Cancer Cells by Inducing Apoptosis and Changing miRNA Expression Profiles vol.15, pp.5, 2014, https://doi.org/10.7314/APJCP.2014.15.5.2169
  2. MicroRNA-10a silencing reverses cisplatin resistance in the A549/cisplatin human lung cancer cell line via the transforming growth factor-β/Smad2/STAT3/STAT5 pathway vol.11, pp.5, 2015, https://doi.org/10.3892/mmr.2015.3181
  3. Gallic Acid Enhancement of Gold Nanoparticle Anticancer Activity in Cervical Cancer Cells vol.16, pp.1, 2015, https://doi.org/10.7314/APJCP.2015.16.1.169
  4. Current Drugs and Drug Targets in Non-Small Cell Lung Cancer: Limitations and Opportunities vol.16, pp.10, 2015, https://doi.org/10.7314/APJCP.2015.16.10.4147
  5. Time - and Concentration - Dependent Effects of Resveratrol on miR 15a and miR16-1 Expression and Apoptosis in the CCRF-CEM Acute Lymphoblastic Leukemia Cell Line vol.16, pp.15, 2015, https://doi.org/10.7314/APJCP.2015.16.15.6463
  6. CAPE Analogs Induce Growth Arrest and Apoptosis in Breast Cancer Cells vol.20, pp.7, 2015, https://doi.org/10.3390/molecules200712576
  7. Anti-tumor effects and cellular mechanisms of resveratrol vol.9, pp.1, 2015, https://doi.org/10.5582/ddt.2015.01007
  8. Comparison of the Anti-inflammatory Effects of Proanthocyanidin, Quercetin, and Damnacanthal on Benzo(a)pyrene Exposed A549 Alveolar Cell Line vol.39, pp.2, 2016, https://doi.org/10.1007/s10753-015-0301-3
  9. Thymoquinone inhibits growth of human medulloblastoma cells by inducing oxidative stress and caspase-dependent apoptosis while suppressing NF-κB signaling and IL-8 expression vol.416, pp.1-2, 2016, https://doi.org/10.1007/s11010-016-2703-4
  10. Caffeic acid phenethyl ester enhances TRAIL-mediated apoptosis via CHOP-induced death receptor 5 upregulation in hepatocarcinoma Hep3B cells vol.418, pp.1-2, 2016, https://doi.org/10.1007/s11010-016-2726-x
  11. Gracilaria edulis exhibit antiproliferative activity against human lung adenocarcinoma cell line A549 without causing adverse toxic effect in vitro and in vivo vol.7, pp.2, 2016, https://doi.org/10.1039/C5FO01094B
  12. Pharmacological perspectives from Brazilian Salvia officinalis (Lamiaceae): antioxidant, and antitumor in mammalian cells vol.88, pp.1, 2016, https://doi.org/10.1590/0001-3765201520150344
  13. Effects of Resveratrol against Lung Cancer: In Vitro and In Vivo Studies vol.9, pp.11, 2017, https://doi.org/10.3390/nu9111231