Advertisement

Targeted Oncology

, Volume 9, Issue 4, pp 295–310 | Cite as

Curcumin and lung cancer—a review

  • Hiren J. Mehta
  • Vipul Patel
  • Ruxana T. SadikotEmail author
Review

Abstract

Curcumin (diferuloylmethane) is the most important component of the spice turmeric and is derived from the rhizome of the East Indian plant Curcuma longa. Curcumin has been used extensively in Ayurvedic medicine for centuries, as it is nontoxic and has a variety of therapeutic properties including antioxidant, analgesic, anti-inflammatory, and antiseptic activities. Recently, curcumin has been widely studied for its anticancer properties via its effects on a variety of biological pathways involved in apoptosis, tumor proliferation, chemo- and radiotherapy sensitization, tumor invasion, and metastases. Curcumin can be an effective adjunct in treating solid organ tumors due to its properties of regulating oncogenes like p53, egr-1, c-myc, bcl-XL, etc.; transcription factors like NF-kB, STAT-3, and AP-1; protein kinases like MAPK; and enzymes like COX and LOX. Lung cancer is the most common malignancy worldwide and a leading cause of cancer-related deaths. Seventy-five percent of lung cancer presents at an advanced stage where the existing treatment is not very effective and may result in tremendous patient morbidity. As a result, there is a significant interest in developing adjunctive chemotherapies to augment currently available treatment protocols, which may allow decreased side effects and toxicity without compromising therapeutic efficacy. Curcumin is one such potential candidate, and this review presents an overview of the current in vitro and in vivo studies of curcumin in lung cancer.

Keywords

Lung cancer Curcumin p53 egr-1 c-myc bcl-XL NF-kB STAT-3 AP-1 MAPK COX LOX 

Notes

Conflict of interest

The authors have no conflicts of interest to declare.

References

  1. 1.
    Siegel R, Naishadham D, Jemal A (2012) Cancer statistics, 2012. CA Cancer J Clin 62(1):10–29PubMedGoogle Scholar
  2. 2.
    Molina JR, Adjei AA, Jett JR (2006) Advances in chemotherapy of non-small cell lung cancer. Chest 130(4):1211–1219PubMedGoogle Scholar
  3. 3.
    Myrdal G et al (2001) Outcome after lung cancer surgery. Factors predicting early mortality and major morbidity. Eur J Cardiothorac Surg 20(4):694–699PubMedGoogle Scholar
  4. 4.
    Scott WJ et al (2007) Treatment of non-small cell lung cancer stage I and stage II: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 132(3 Suppl):234S–242SPubMedGoogle Scholar
  5. 5.
    Pfister DG et al (2004) American Society of Clinical Oncology treatment of unresectable non-small-cell lung cancer guideline: update 2003. J Clin Oncol 22(2):330–353PubMedGoogle Scholar
  6. 6.
    Azzoli CG et al (2011) Focused Update of 2009 American Society of Clinical Oncology clinical practice guideline update on chemotherapy for stage IV non-small-cell lung cancer. J Clin Oncol 29(28):3825–3831PubMedCentralPubMedGoogle Scholar
  7. 7.
    Fukuoka M (2001) State of the art of non-small-cell lung cancer in the new millennium. Oncology (Williston Park) 15(3 Suppl 6):9–11Google Scholar
  8. 8.
    Johnson DH (2000) Locally advanced, unresectable non-small cell lung cancer: new treatment strategies. Chest 117(4 Suppl 1):123S–126SPubMedGoogle Scholar
  9. 9.
    Arriagada R et al (2010) Long-term results of the international adjuvant lung cancer trial evaluating adjuvant Cisplatin-based chemotherapy in resected lung cancer. J Clin Oncol 28(1):35–42PubMedGoogle Scholar
  10. 10.
    Kato H et al (2005) Postoperative adjuvant therapy for completely resected early-stage non-small cell lung cancer. Int J Clin Oncol 10(3):157–164PubMedGoogle Scholar
  11. 11.
    Baggstrom MQ et al (2007) Third-generation chemotherapy agents in the treatment of advanced non-small cell lung cancer: a meta-analysis. J Thorac Oncol 2(9):845–853PubMedGoogle Scholar
  12. 12.
    Chattopadhyay I et al (2004) Mechanism of antiulcer effect of Neem (Azadirachta indica) leaf extract: effect on H + -K + -ATPase, oxidative damage and apoptosis. Inflammopharmacology 12(2):153–176PubMedGoogle Scholar
  13. 13.
    Jurenka JS (2009) Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research. Altern Med Rev 14(2):141–153PubMedGoogle Scholar
  14. 14.
    Goel A, Aggarwal BB (2010) Curcumin, the golden spice from Indian saffron, is a chemosensitizer and radiosensitizer for tumors and chemoprotector and radioprotector for normal organs. Nutr Cancer 62(7):919–930PubMedGoogle Scholar
  15. 15.
    El-Deiry WS et al (1993) WAF1, a potential mediator of p53 tumor suppression. Cell 75(4):817–825PubMedGoogle Scholar
  16. 16.
    Park MJ et al (2002) Curcumin inhibits cell cycle progression of immortalized human umbilical vein endothelial (ECV304) cells by up-regulating cyclin-dependent kinase inhibitor, p21WAF1/CIP1, p27KIP1 and p53. Int J Oncol 21(2):379–383PubMedGoogle Scholar
  17. 17.
    Singh S, Aggarwal BB (1995) Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane) [corrected]. J Biol Chem 270(42):24995–25000PubMedGoogle Scholar
  18. 18.
    Jobin C et al (1999) Curcumin blocks cytokine-mediated NF-kappa B activation and proinflammatory gene expression by inhibiting inhibitory factor I-kappa B kinase activity. J Immunol 163(6):3474–3483PubMedGoogle Scholar
  19. 19.
    Dikshit P et al (2006) Curcumin induces stress response, neurite outgrowth and prevent NF-kappaB activation by inhibiting the proteasome function. Neurotox Res 9(1):29–37PubMedGoogle Scholar
  20. 20.
    Shishodia S et al (2003) Curcumin (diferuloylmethane) down-regulates cigarette smoke-induced NF-kappaB activation through inhibition of IkappaBalpha kinase in human lung epithelial cells: correlation with suppression of COX-2, MMP-9 and cyclin D1. Carcinogenesis 24(7):1269–1279PubMedGoogle Scholar
  21. 21.
    Bharti AC, Donato N, Aggarwal BB (2003) Curcumin (diferuloylmethane) inhibits constitutive and IL-6-inducible STAT3 phosphorylation in human multiple myeloma cells. J Immunol 171(7):3863–3871PubMedGoogle Scholar
  22. 22.
    Li WQ, Dehnade F, Zafarullah M (2001) Oncostatin M-induced matrix metalloproteinase and tissue inhibitor of metalloproteinase-3 genes expression in chondrocytes requires Janus kinase/STAT signaling pathway. J Immunol 166(5):3491–3498PubMedGoogle Scholar
  23. 23.
    Karin M, Liu Z, Zandi E (1997) AP-1 function and regulation. Curr Opin Cell Biol 9(2):240–246PubMedGoogle Scholar
  24. 24.
    Huang TS, Lee SC, Lin JK (1991) Suppression of c-Jun/AP-1 activation by an inhibitor of tumor promotion in mouse fibroblast cells. Proc Natl Acad Sci U S A 88(12):5292–5296PubMedCentralPubMedGoogle Scholar
  25. 25.
    Bierhaus A et al (1997) The dietary pigment curcumin reduces endothelial tissue factor gene expression by inhibiting binding of AP-1 to the DNA and activation of NF-kappa B. Thromb Haemost 77(4):772–782PubMedGoogle Scholar
  26. 26.
    Marcu MG et al (2006) Curcumin is an inhibitor of p300 histone acetyltransferase. Med Chem 2(2):169–174PubMedGoogle Scholar
  27. 27.
    Balasubramanyam K et al (2004) Curcumin, a novel p300/CREB-binding protein-specific inhibitor of acetyltransferase, represses the acetylation of histone/nonhistone proteins and histone acetyltransferase-dependent chromatin transcription. J Biol Chem 279(49):51163–51171PubMedGoogle Scholar
  28. 28.
    Pendurthi UR, Rao LV (2000) Suppression of transcription factor Egr-1 by curcumin. Thromb Res 97(4):179–189PubMedGoogle Scholar
  29. 29.
    Balogun E et al (2003) Curcumin activates the haem oxygenase-1 gene via regulation of Nrf2 and the antioxidant-responsive element. Biochem J 371(Pt 3):887–895PubMedCentralPubMedGoogle Scholar
  30. 30.
    Cowley S et al (1994) Activation of MAP kinase kinase is necessary and sufficient for PC12 differentiation and for transformation of NIH 3 T3 cells. Cell 77(6):841–852PubMedGoogle Scholar
  31. 31.
    Minden A et al (1994) Differential activation of ERK and JNK mitogen-activated protein kinases by Raf-1 and MEKK. Science 266(5191):1719–1723PubMedGoogle Scholar
  32. 32.
    Kim KH et al (2005) The inhibitory effect of curcumin on the growth of human colon cancer cells (HT-29, WiDr) in vitro. Korean J Gastroenterol 45(4):277–284PubMedGoogle Scholar
  33. 33.
    Reddy S, Aggarwal BB (1994) Curcumin is a non-competitive and selective inhibitor of phosphorylase kinase. FEBS Lett 341(1):19–22PubMedGoogle Scholar
  34. 34.
    Subbaramaiah K, Dannenberg AJ (2003) Cyclooxygenase 2: a molecular target for cancer prevention and treatment. Trends Pharmacol Sci 24(2):96–102PubMedGoogle Scholar
  35. 35.
    Plummer SM et al (1999) Inhibition of cyclo-oxygenase 2 expression in colon cells by the chemopreventive agent curcumin involves inhibition of NF-kappaB activation via the NIK/IKK signalling complex. Oncogene 18(44):6013–6020PubMedGoogle Scholar
  36. 36.
    Chen H et al (1999) Curcumin inhibits cell proliferation by interfering with the cell cycle and inducing apoptosis in colon carcinoma cells. Anticancer Res 19(5A):3675–3680PubMedGoogle Scholar
  37. 37.
    Hong J et al (2004) Modulation of arachidonic acid metabolism by curcumin and related beta-diketone derivatives: effects on cytosolic phospholipase A(2), cyclooxygenases and 5-lipoxygenase. Carcinogenesis 25(9):1671–1679PubMedGoogle Scholar
  38. 38.
    Ohene-Abuakwa Y et al (2000) Expression of the E-cadherin/catenin (alpha-, beta-, and gamma-) complex correlates with the macroscopic appearance of early gastric cancer. J Pathol 192(4):433–439PubMedGoogle Scholar
  39. 39.
    Kumar A et al (1998) Curcumin (diferuloylmethane) inhibition of tumor necrosis factor (TNF)-mediated adhesion of monocytes to endothelial cells by suppression of cell surface expression of adhesion molecules and of nuclear factor-kappaB activation. Biochem Pharmacol 55(6):775–783PubMedGoogle Scholar
  40. 40.
    Jaiswal AS et al (2002) Beta-catenin-mediated transactivation and cell-cell adhesion pathways are important in curcumin (diferuylmethane)-induced growth arrest and apoptosis in colon cancer cells. Oncogene 21(55):8414–8427PubMedGoogle Scholar
  41. 41.
    Aggarwal BB (2003) Signalling pathways of the TNF superfamily: a double-edged sword. Nat Rev Immunol 3(9):745–756PubMedGoogle Scholar
  42. 42.
    Shishodia S et al (2005) Curcumin (diferuloylmethane) inhibits constitutive NF-kappaB activation, induces G1/S arrest, suppresses proliferation, and induces apoptosis in mantle cell lymphoma. Biochem Pharmacol 70(5):700–713PubMedGoogle Scholar
  43. 43.
    Danial NN, Korsmeyer SJ (2004) Cell death: critical control points. Cell 116(2):205–219PubMedGoogle Scholar
  44. 44.
    Debatin KM, Krammer PH (2004) Death receptors in chemotherapy and cancer. Oncogene 23(16):2950–2966PubMedGoogle Scholar
  45. 45.
    Bergman PJ, Harris D (1997) Radioresistance, chemoresistance, and apoptosis resistance. The past, present, and future. Vet Clin N Am Small Anim Pract 27(1):47–57Google Scholar
  46. 46.
    Tan TT et al (2005) Key roles of BIM-driven apoptosis in epithelial tumors and rational chemotherapy. Cancer Cell 7(3):227–238PubMedGoogle Scholar
  47. 47.
    Decaudin D et al (1998) Mitochondria in chemotherapy-induced apoptosis: a prospective novel target of cancer therapy (review). Int J Oncol 12(1):141–152PubMedGoogle Scholar
  48. 48.
    Piro LD (2004) Apoptosis, Bcl-2 antisense, and cancer therapy. Oncology (Williston Park) 18(13 Suppl 10):5–10Google Scholar
  49. 49.
    Choudhury D, et al (2013) Apigenin shows synergistic anticancer activity with curcumin by binding at different sites of tubulin. BiochimieGoogle Scholar
  50. 50.
    Zhang J et al (2010) Curcumin promotes apoptosis in human lung adenocarcinoma cells through miR-186* signaling pathway. Oncol Rep 24(5):1217–1223PubMedGoogle Scholar
  51. 51.
    Zhang J et al (2010) Curcumin promotes apoptosis in A549/DDP multidrug-resistant human lung adenocarcinoma cells through an miRNA signaling pathway. Biochem Biophys Res Commun 399(1):1–6PubMedGoogle Scholar
  52. 52.
    Tang N, Zhang J, Du Y (2010) Curcumin promoted the apoptosis of cisplatin-resistant human lung carcinoma cells A549/DDP through down-regulating miR-186*. Zhongguo Fei Ai Za Zhi 13(4):301–306PubMedGoogle Scholar
  53. 53.
    Saha A et al (2010) Apoptosis of human lung cancer cells by curcumin mediated through up-regulation of “growth arrest and DNA damage inducible genes 45 and 153”. Biol Pharm Bull 33(8):1291–1299PubMedGoogle Scholar
  54. 54.
    Weng SH et al (2012) Enhancement of mitomycin C-induced cytotoxicity by curcumin results from down-regulation of MKK1/2-ERK1/2-mediated thymidine phosphorylase expression. Basic Clin Pharmacol Toxicol 110(3):298–306PubMedGoogle Scholar
  55. 55.
    Chen QY et al (2012) Lysosomal membrane permeabilization is involved in curcumin-induced apoptosis of A549 lung carcinoma cells. Mol Cell Biochem 359(1–2):389–398PubMedGoogle Scholar
  56. 56.
    Yang CL et al (2012) Curcumin induces small cell lung cancer NCI-H446 cell apoptosis via the reactive oxygen species-mediated mitochondrial pathway and not the cell death receptor pathway. DNA Cell Biol 31(2):139–150PubMedGoogle Scholar
  57. 57.
    Chen QY et al (2010) Curcumin induces mitochondria pathway mediated cell apoptosis in A549 lung adenocarcinoma cells. Oncol Rep 23(5):1285–1292PubMedGoogle Scholar
  58. 58.
    Wu SH et al (2010) Curcumin induces apoptosis in human non-small cell lung cancer NCI-H460 cells through ER stress and caspase cascade- and mitochondria-dependent pathways. Anticancer Res 30(6):2125–2133PubMedGoogle Scholar
  59. 59.
    Pongrakhananon V et al (2010) Curcumin sensitizes non-small cell lung cancer cell anoikis through reactive oxygen species-mediated Bcl-2 downregulation. Apoptosis 15(5):574–585PubMedGoogle Scholar
  60. 60.
    Chen Q et al (2009) Cytoskeleton disorganization during apoptosis induced by curcumin in A549 lung adenocarcinoma cells. Planta Med 75(8):808–813PubMedGoogle Scholar
  61. 61.
    Lin SS et al (2008) DNA damage and endoplasmic reticulum stress mediated curcumin-induced cell cycle arrest and apoptosis in human lung carcinoma A-549 cells through the activation caspases cascade- and mitochondrial-dependent pathway. Cancer Lett 272(1):77–90PubMedGoogle Scholar
  62. 62.
    Lev-Ari S et al (2006) Inhibition of pancreatic and lung adenocarcinoma cell survival by curcumin is associated with increased apoptosis, down-regulation of COX-2 and EGFR and inhibition of Erk1/2 activity. Anticancer Res 26(6B):4423–4430PubMedGoogle Scholar
  63. 63.
    Moghaddam SJ et al (2009) Curcumin inhibits COPD-like airway inflammation and lung cancer progression in mice. Carcinogenesis 30(11):1949–1956PubMedCentralPubMedGoogle Scholar
  64. 64.
    Augenlicht L et al (1999) Colonic cell proliferation, differentiation, and apoptosis. Adv Exp Med Biol 470:15–22PubMedGoogle Scholar
  65. 65.
    Liu H et al (2012) T63, a new 4-arylidene curcumin analogue, induces cell cycle arrest and apoptosis through activation of the reactive oxygen species-FOXO3a pathway in lung cancer cells. Free Radic Biol Med 53(12):2204–2217PubMedGoogle Scholar
  66. 66.
    Ravindran J, Prasad S, Aggarwal BB (2009) Curcumin and cancer cells: how many ways can curry kill tumor cells selectively? AAPS J 11(3):495–510PubMedCentralPubMedGoogle Scholar
  67. 67.
    Chen L et al (2010) Curcumin modulates eukaryotic initiation factors in human lung adenocarcinoma epithelial cells. Mol Biol Rep 37(7):3105–3110PubMedGoogle Scholar
  68. 68.
    Yang CL et al (2012) Curcumin blocks small cell lung cancer cells migration, invasion, angiogenesis, cell cycle and neoplasia through Janus kinase-STAT3 signalling pathway. PLoS ONE 7(5):e37960PubMedCentralPubMedGoogle Scholar
  69. 69.
    Alexandrow MG et al (2012) Curcumin: a novel Stat3 pathway inhibitor for chemoprevention of lung cancer. Eur J Cancer Prev 21(5):407–412PubMedCentralPubMedGoogle Scholar
  70. 70.
    Datta R, Halder SK, Zhang B (2013) Role of TGF-beta signaling in curcumin-mediated inhibition of tumorigenicity of human lung cancer cells. J Cancer Res Clin Oncol 139(4):563–572PubMedGoogle Scholar
  71. 71.
    Xu Y et al (2012) Curcumin inhibits tumor proliferation induced by neutrophil elastase through the upregulation of alpha1-antitrypsin in lung cancer. Mol Oncol 6(4):405–417PubMedGoogle Scholar
  72. 72.
    Luo F et al (2011) Low-dose curcumin leads to the inhibition of tumor growth via enhancing CTL-mediated antitumor immunity. Int Immunopharmacol 11(9):1234–1240PubMedGoogle Scholar
  73. 73.
    Folkman J (1992) The role of angiogenesis in tumor growth. Semin Cancer Biol 3(2):65–71PubMedGoogle Scholar
  74. 74.
    Woodhouse EC, Chuaqui RF, Liotta LA (1997) General mechanisms of metastasis. Cancer 80(8 Suppl):1529–1537PubMedGoogle Scholar
  75. 75.
    Fidler IJ (1999) Critical determinants of cancer metastasis: rationale for therapy. Cancer Chemother Pharmacol 43(Suppl):S3–S10PubMedGoogle Scholar
  76. 76.
    Wyckoff JB et al (2000) A critical step in metastasis: in vivo analysis of intravasation at the primary tumor. Cancer Res 60(9):2504–2511PubMedGoogle Scholar
  77. 77.
    Cao Y, Liu Q (2007) Therapeutic targets of multiple angiogenic factors for the treatment of cancer and metastasis. Adv Cancer Res 97:203–224PubMedGoogle Scholar
  78. 78.
    Chen QY et al (2012) Expression analysis of Cdc42 in lung cancer and modulation of its expression by curcumin in lung cancer cell lines. Int J Oncol 40(5):1561–1568PubMedGoogle Scholar
  79. 79.
    Lin SS et al (2009) Curcumin inhibits the migration and invasion of human A549 lung cancer cells through the inhibition of matrix metalloproteinase-2 and -9 and vascular endothelial growth factor (VEGF). Cancer Lett 285(2):127–133PubMedGoogle Scholar
  80. 80.
    Chen HW et al (2008) Curcumin inhibits lung cancer cell invasion and metastasis through the tumor suppressor HLJ1. Cancer Res 68(18):7428–7438PubMedGoogle Scholar
  81. 81.
    Chen HW et al (2004) Anti-invasive gene expression profile of curcumin in lung adenocarcinoma based on a high throughput microarray analysis. Mol Pharmacol 65(1):99–110PubMedGoogle Scholar
  82. 82.
    Ho CC et al (2008) TREM-1 expression in tumor-associated macrophages and clinical outcome in lung cancer. Am J Respir Crit Care Med 177(7):763–770PubMedGoogle Scholar
  83. 83.
    Yuan Z et al (2012) Curcumin mediated epigenetic modulation inhibits TREM-1 expression in response to lipopolysaccharide. Int J Biochem Cell Biol 44(11):2032–2043PubMedGoogle Scholar
  84. 84.
    Bachmeier BE et al (2010) Novel aspects for the application of curcumin in chemoprevention of various cancers. Front Biosci (Schol Ed) 2:697–717Google Scholar
  85. 85.
    Bar-Sela G, Epelbaum R, Schaffer M (2010) Curcumin as an anti-cancer agent: review of the gap between basic and clinical applications. Curr Med Chem 17(3):190–197PubMedGoogle Scholar
  86. 86.
    Ichiki K et al (2000) Regulation of activator protein-1 activity in the mediastinal lymph node metastasis of lung cancer. Clin Exp Metastasis 18(7):539–545PubMedGoogle Scholar
  87. 87.
    Tung YT et al (2011) Curcumin reduces pulmonary tumorigenesis in vascular endothelial growth factor (VEGF)-overexpressing transgenic mice. Mol Nutr Food Res 55(7):1036–1043PubMedGoogle Scholar
  88. 88.
    Markman M et al (2004) Survival following the documentation of platinum and taxane resistance in ovarian cancer: a single institution experience involving multiple phase 2 clinical trials. Gynecol Oncol 93(3):699–701PubMedGoogle Scholar
  89. 89.
    Borst P, Rottenberg S, Jonkers J (2008) How do real tumors become resistant to cisplatin? Cell Cycle 7(10):1353–1359PubMedGoogle Scholar
  90. 90.
    Armstrong DK (2002) Relapsed ovarian cancer: challenges and management strategies for a chronic disease. Oncologist 7(Suppl 5):20–28PubMedGoogle Scholar
  91. 91.
    Markman M (2008) Pharmaceutical management of ovarian cancer: current status. Drugs 68(6):771–789PubMedGoogle Scholar
  92. 92.
    Herzog TJ, Pothuri B (2006) Ovarian cancer: a focus on management of recurrent disease. Nat Clin Pract Oncol 3(11):604–611PubMedGoogle Scholar
  93. 93.
    Ko JC et al (2011) Curcumin enhances the mitomycin C-induced cytotoxicity via downregulation of MKK1/2-ERK1/2-mediated Rad51 expression in non-small cell lung cancer cells. Toxicol Appl Pharmacol 255(3):327–338PubMedGoogle Scholar
  94. 94.
    Tsai MS et al (2011) Synergistic effect of curcumin and cisplatin via down-regulation of thymidine phosphorylase and excision repair cross-complementary 1 (ERCC1). Mol Pharmacol 80(1):136–146PubMedGoogle Scholar
  95. 95.
    Sen S, Sharma H, Singh N (2005) Curcumin enhances Vinorelbine mediated apoptosis in NSCLC cells by the mitochondrial pathway. Biochem Biophys Res Commun 331(4):1245–1252PubMedGoogle Scholar
  96. 96.
    Shi HS et al (2012) A systemic administration of liposomal curcumin inhibits radiation pneumonitis and sensitizes lung carcinoma to radiation. Int J Nanomedicine 7:2601–2611PubMedCentralPubMedGoogle Scholar
  97. 97.
    Lee JC et al (2010) Dietary curcumin increases antioxidant defenses in lung, ameliorates radiation-induced pulmonary fibrosis, and improves survival in mice. Radiat Res 173(5):590–601PubMedCentralPubMedGoogle Scholar
  98. 98.
    Ye MX et al (2012) Curcumin reverses cis-platin resistance and promotes human lung adenocarcinoma A549/DDP cell apoptosis through HIF-1alpha and caspase-3 mechanisms. Phytomedicine 19(8–9):779–787PubMedGoogle Scholar
  99. 99.
    Yin H et al (2012) Synergistic antitumor efficiency of docetaxel and curcumin against lung cancer. Acta Biochim Biophys Sin (Shanghai) 44(2):147–153Google Scholar
  100. 100.
    Zhang BY et al (2012) Protective effect of curcumin against formaldehyde-induced genotoxicity in A549 cell lines. J Appl ToxicolGoogle Scholar
  101. 101.
    Rocks N et al (2012) Curcumin-cyclodextrin complexes potentiate gemcitabine effects in an orthotopic mouse model of lung cancer. Br J Cancer 107(7):1083–1092PubMedCentralPubMedGoogle Scholar
  102. 102.
    Lee JY et al (2011) Curcumin induces EGFR degradation in lung adenocarcinoma and modulates p38 activation in intestine: the versatile adjuvant for gefitinib therapy. PLoS ONE 6(8):e23756PubMedCentralPubMedGoogle Scholar
  103. 103.
    Andjelkovic T et al (2008) Synergistic effects of the purine analog sulfinosine and curcumin on the multidrug resistant human non-small cell lung carcinoma cell line (NCI-H460/R). Cancer Biol Ther 7(7):1024–1032PubMedGoogle Scholar
  104. 104.
    Lee J et al (2006) Interferon-alpha resistance can be reversed by inhibition of IFN-alpha-induced COX-2 expression potentially via STAT1 activation in A549 cells. Oncol Rep 15(6):1541–1549PubMedGoogle Scholar
  105. 105.
    Kelloff GJ et al (1994) Mechanistic considerations in chemopreventive drug development. J Cell Biochem Suppl 20:1–24PubMedGoogle Scholar
  106. 106.
    Thapliyal R, Maru GB (2001) Inhibition of cytochrome P450 isozymes by curcumins in vitro and in vivo. Food Chem Toxicol 39(6):541–547PubMedGoogle Scholar
  107. 107.
    Chen X et al (1997) Inhibition of farnesyl protein transferase by monoterpene, curcumin derivatives and gallotannin. Anticancer Res 17(4A):2555–2564PubMedGoogle Scholar
  108. 108.
    Sajithlal GB, Chithra P, Chandrakasan G (1998) Effect of curcumin on the advanced glycation and cross-linking of collagen in diabetic rats. Biochem Pharmacol 56(12):1607–1614PubMedGoogle Scholar
  109. 109.
    Malhotra A, Nair P, Dhawan DK (2012) Premature mitochondrial senescence and related ultrastructural changes during lung carcinogenesis modulation by curcumin and resveratrol. Ultrastruct Pathol 36(3):179–184PubMedGoogle Scholar
  110. 110.
    Wahlstrom B, Blennow G (1978) A study on the fate of curcumin in the rat. Acta Pharmacol Toxicol (Copenh) 43(2):86–92Google Scholar
  111. 111.
    Pan MH, Huang TM, Lin JK (1999) Biotransformation of curcumin through reduction and glucuronidation in mice. Drug Metab Dispos 27(4):486–494PubMedGoogle Scholar
  112. 112.
    Maiti K et al (2007) Curcumin-phospholipid complex: preparation, therapeutic evaluation and pharmacokinetic study in rats. Int J Pharm 330(1–2):155–163PubMedGoogle Scholar
  113. 113.
    Shoba G et al (1998) Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med 64(4):353–356PubMedGoogle Scholar
  114. 114.
    Mosley CA, Liotta DC, Snyder JP (2007) Highly active anticancer curcumin analogues. Adv Exp Med Biol 595:77–103PubMedGoogle Scholar
  115. 115.
    Ma Z et al (2007) High-performance liquid chromatography analysis of curcumin in rat plasma: application to pharmacokinetics of polymeric micellar formulation of curcumin. Biomed Chromatogr 21(5):546–552PubMedGoogle Scholar
  116. 116.
    Bisht S et al (2007) Polymeric nanoparticle-encapsulated curcumin (“nanocurcumin”): a novel strategy for human cancer therapy. J Nanobiotechnology 5:3PubMedCentralPubMedGoogle Scholar
  117. 117.
    Liu A et al (2006) Validated LC/MS/MS assay for curcumin and tetrahydrocurcumin in rat plasma and application to pharmacokinetic study of phospholipid complex of curcumin. J Pharm Biomed Anal 40(3):720–727PubMedGoogle Scholar
  118. 118.
    Curcumin—FDA GRAS reportGoogle Scholar
  119. 119.
    Lopez-Lazaro M (2008) Anticancer and carcinogenic properties of curcumin: considerations for its clinical development as a cancer chemopreventive and chemotherapeutic agent. Mol Nutr Food Res 52(Suppl 1):S103–S127PubMedGoogle Scholar
  120. 120.
    National Toxicology P (1993) NTP toxicology and carcinogenesis studies of turmeric oleoresin (CAS No. 8024-37-1) (major component 79 %–85% curcumin, CAS No. 458-37-7) in F344/N rats and B6C3F1 mice (feed studies). Natl Toxicol Program Tech Rep Ser 427:1–275Google Scholar
  121. 121.
    Somasundaram S et al (2002) Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer. Cancer Res 62(13):3868–3875PubMedGoogle Scholar
  122. 122.
    Sandur SK et al (2007) Role of pro-oxidants and antioxidants in the anti-inflammatory and apoptotic effects of curcumin (diferuloylmethane). Free Radic Biol Med 43(4):568–580PubMedCentralPubMedGoogle Scholar
  123. 123.
    Kanai M et al (2011) A phase I/II study of gemcitabine-based chemotherapy plus curcumin for patients with gemcitabine-resistant pancreatic cancer. Cancer Chemother Pharmacol 68(1):157–164PubMedGoogle Scholar
  124. 124.
    Kanai M et al (2013) A phase I study investigating the safety and pharmacokinetics of highly bioavailable curcumin (Theracurmin) in cancer patients. Cancer Chemother Pharmacol 71(6):1521–1530PubMedGoogle Scholar
  125. 125.
    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(1):40–59PubMedCentralPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland (outside the USA) 2014

Authors and Affiliations

  • Hiren J. Mehta
    • 1
  • Vipul Patel
    • 1
  • Ruxana T. Sadikot
    • 1
    • 2
    Email author
  1. 1.Division of Pulmonary, Critical Care and Sleep Medicine, Department of MedicineUniversity of FloridaGainesvilleUSA
  2. 2.Department of Veterans AffairsMalcolm Randall NF/SG VHSGainesvilleUSA

Personalised recommendations