Advertisement

Role of Curcumin: A Suppressor of NF-κB Activity in Hepatocellular Carcinoma

  • Saipriya Lammata
  • Mundla Srilatha
  • Ganji Purnachandra Nagaraju
Chapter
First Online:

Abstract

Leading as the third cause of cancer-related deaths in the world, hepatocellular carcinoma (HCC) is an aggressive cancer that offers little to no treatment for patients in the advanced stages due to the frequency of recurrence. Moreover, the upregulation of the nuclear factor-kappaB (NF-κB) signaling pathway leads to uncontrolled cell growth, metastasis, and resistance in HCC. Curcumin, a polyphenol derived from turmeric, has been found to inhibit NF-κB activity in HCC and to present other antitumor properties such as anti-proliferation, anti-inflammation, and anti-angiogenic properties. Furthermore, curcumin also acts as a collaborative agent with available chemotherapy and radiotherapy. Working against the drawbacks of poor bioavailability and rapid metabolism, researchers are discovering new ways of encapsulating curcumin in order to exhibit its full efficacy against HCC metastasis.

Keywords

Curcumin NF-κB pathway Hepatocellular carcinoma Angiogenesis Chemotherapy 

Abbreviations

Akt

Protein kinase B

bFGF

Basic fibroblast growth factors

COX-2

Cyclooxygenase-2

FLHCC

Fibrolamellar hepatocellular carcinoma

HBx

Protein X of the hepatitis B virus

HCC

Hepatocellular Carcinoma

HHC

Hexahydrocurcumin

IκBs

Inhibitors of NF-κB

IKK

IκB kinase

NF-κB

Nuclear Factor-kappaB

PCD

Programmed cell death

PEI

Percutaneous ethanol injection

PPAR-γ

Peroxisome proliferator-activated receptor-γ

THC

Tetrahydrocurcumin

VEGF

Vascular endothelial growth factor

This is a preview of subscription content, log in to check access.

References

  1. 1.
    Afrin R, Arumugam S, Rahman A, Wahed MII, Karuppagounder V, Harima M, Suzuki H, Miyashita S, Suzuki K, Yoneyama H (2017) Curcumin ameliorates liver damage and progression of NASH in NASH-HCC mouse model possibly by modulating HMGB1-NF-κB translocation. Int Immunopharmacol 44:174–182CrossRefPubMedGoogle Scholar
  2. 2.
    Aggarwal BB, Kumar A, Bharti AC (2003) Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res 23(1/A):363–398PubMedGoogle Scholar
  3. 3.
    Amornwachirabodee K, Chiablaem K, Wacharasindhu S, Lirdprapamongkol K, Svasti J, Vchirawongkwin V, Wanichwecharungruang SP (2012) Paclitaxel delivery using carrier made from curcumin derivative: synergism between carrier and the loaded drug for effective cancer treatment. J Pharm Sci 101(10):3779–3786CrossRefPubMedGoogle Scholar
  4. 4.
    Anand P, Sundaram C, Jhurani S, Kunnumakkara AB, Aggarwal BB (2008) Curcumin and cancer: an “old-age” disease with an “age-old” solution. Cancer Lett 267(1):133–164CrossRefPubMedGoogle Scholar
  5. 5.
    Arbiser JL, Klauber N, Rohan R, Van Leeuwen R, Huang M-T, Fisher C, Flynn E, Byers HR (1998) Curcumin is an in vivo inhibitor of angiogenesis. Mol Med 4(6):376PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Baldwin AS (2001) Control of oncogenesis and cancer therapy resistance by the transcription factor NF-κB. J Clin Invest 107(3):241–246CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Begum AN, Jones MR, Lim GP, Morihara T, Kim P, Heath DD, Rock CL, Pruitt MA, Yang F, Hudspeth B (2008) Curcumin structure-function, bioavailability, and efficacy in models of neuroinflammation and Alzheimer’s disease. J Pharmacol Exp Ther 326(1):196–208CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Bhandarkar SS, Arbiser JL (2007) Curcumin as an inhibitor of angiogenesis. In: The molecular targets and therapeutic uses of curcumin in health and disease. Springer, Dordrecht, pp 185–195Google Scholar
  9. 9.
    Blum HE (2011) Hepatocellular carcinoma: HCC. Hepat Mon 11(2):69PubMedPubMedCentralGoogle Scholar
  10. 10.
    Bruix J, Llovet JM (2002) Prognostic prediction and treatment strategy in hepatocellular carcinoma. Hepatology 35(3):519–524CrossRefPubMedGoogle Scholar
  11. 11.
    Bruix J, Sherman M (2011) Management of hepatocellular carcinoma: an update. Hepatology 53(3):1020–1022CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Bubici C, Papa S, Pham C, Zazzeroni F, Franzoso G (2006) The NF-κB-mediated control of ROS and JNK signaling. Histol Histopathol 21(1):69–80Google Scholar
  13. 13.
    Chintana P (2013) Role of curcumin on tumor angiogenesis in hepatocellular carcinoma. Naresuan Univ J Sci Technol 16(3):239–254Google Scholar
  14. 14.
    Dolcet X, Llobet D, Pallares J, Matias-Guiu X (2005) NF-κB in development and progression of human cancer. Virchows Arch 446(5):475–482CrossRefPubMedGoogle Scholar
  15. 15.
    Hatcher H, Planalp R, Cho J, Torti F, Torti S (2008) Curcumin: from ancient medicine to current clinical trials. Cell Mol Life Sci 65(11):1631–1652CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Hsu F-T, Liu Y-C, Liu T-T, Hwang J-J (2015) Curcumin sensitizes hepatocellular carcinoma cells to radiation via suppression of radiation-induced NF-κB activity. Biomed Res Int. 363671–363677Google Scholar
  17. 17.
    Ireson CR, Jones DJ, Orr S, Coughtrie MW, Boocock DJ, Williams ML, Farmer PB, Steward WP, Gescher AJ (2002) Metabolism of the cancer chemopreventive agent curcumin in human and rat intestine. Cancer Epidemiol Prev Biomark 11(1):105–111Google Scholar
  18. 18.
    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)Google Scholar
  19. 19.
    Kojima M, Morisaki T, Sasaki N, Nakano K, Mibu R, Tanaka M, Katano M (2004) Increased nuclear factor-kB activation in human colorectal carcinoma and its correlation with tumor progression. Anticancer Res 24(2B):675–682PubMedGoogle Scholar
  20. 20.
    Kunnumakkara AB, Anand P, Aggarwal BB (2008) Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins. Cancer Lett 269(2):199–225CrossRefPubMedGoogle Scholar
  21. 21.
    Kurien BT, Scofield RH (2009) Oral administration of heat-solubilized curcumin for potentially increasing curcumin bioavailability in experimental animals. Int J Cancer 125(8):1992–1993CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Li W, Tan D, Zenali MJ, Brown RE (2010) Constitutive activation of nuclear factor-kappa B (NF-κB) signaling pathway in fibrolamellar hepatocellular carcinoma. Int J Clin Exp Pathol 3(3):238–243Google Scholar
  23. 23.
    Liang G, Yang S, Zhou H, Shao L, Huang K, Xiao J, Huang Z, Li X (2009) Synthesis, crystal structure and anti-inflammatory properties of curcumin analogues. Eur J Med Chem 44(2):915–919CrossRefPubMedGoogle Scholar
  24. 24.
    Lv FH, Yin HL, He YQ, Wu HM, Kong J, Chai XY, Zhang SR (2016) Effects of curcumin on the apoptosis of cardiomyocytes and the expression of NF-κB, PPAR-γ and Bcl-2 in rats with myocardial infarction injury. Exp Ther Med 12(6):3877–3884CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Maheshwari RK, Singh AK, Gaddipati J, Srimal RC (2006) Multiple biological activities of curcumin: a short review. Life Sci 78(18):2081–2087CrossRefPubMedGoogle Scholar
  26. 26.
    Muriel P (2009) NF-κB in liver diseases: a target for drug therapy. J Appl Toxicol 29(2):91–100CrossRefPubMedGoogle Scholar
  27. 27.
    Naugler WE, Karin M (2008) NF-κB and cancer—identifying targets and mechanisms. Curr Opin Genet Dev 18(1):19–26CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Notarbartolo M, Poma P, Perri D, Dusonchet L, Cervello M, D’Alessandro N (2005) Antitumor effects of curcumin, alone or in combination with cisplatin or doxorubicin, on human hepatic cancer cells. Analysis of their possible relationship to changes in NF-κB activation levels and in IAP gene expression. Cancer Lett 224(1):53–65CrossRefPubMedGoogle Scholar
  29. 29.
    Paul AG (2005) NF-κB: a novel therapeutic target for cancer. Eukaryon 1(1):2Google Scholar
  30. 30.
    Prasad S, Tyagi AK, Aggarwal BB (2014) Recent developments in delivery, bioavailability, absorption and metabolism of curcumin: the golden pigment from golden spice. Cancer Res Treat: Off J Korean Cancer Assoc 46(1):2–18CrossRefGoogle Scholar
  31. 31.
    Pulido-Moran M, Moreno-Fernandez J, Ramirez-Tortosa C, Ramirez-Tortosa M (2016) Curcumin and health. Molecules 21(3):264CrossRefGoogle Scholar
  32. 32.
    Ramesh V, Selvarasu K, Pandian J, Myilsamy S, Shanmugasundaram C, Ganesan K (2016) NFκB activation demarcates a subset of hepatocellular carcinoma patients for targeted therapy. Cell Oncol 39(6):523–536CrossRefGoogle Scholar
  33. 33.
    Ryder SD (2003) Guidelines for the diagnosis and treatment of hepatocellular carcinoma (HCC) in adults. Gut 52(suppl 3):iii1–iii8PubMedPubMedCentralGoogle Scholar
  34. 34.
    Sandur SK, Pandey MK, Sung B, Ahn KS, Murakami A, Sethi G, Limtrakul P, Badmaev V, Aggarwal BB (2007) Curcumin, demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin and turmerones differentially regulate anti-inflammatory and anti-proliferative responses through a ROS-independent mechanism. Carcinogenesis 28(8):1765–1773CrossRefPubMedGoogle Scholar
  35. 35.
    Senftleben U, Cao Y, Xiao G, Greten FR, Krähn G, Bonizzi G, Chen Y, Hu Y, Fong A, Sun S-C (2001) Activation by IKKα of a second, evolutionary conserved, NF-κB signaling pathway. Science 293(5534):1495–1499CrossRefPubMedGoogle Scholar
  36. 36.
    Shehzad A, Khan S, Shehzad O, Lee Y (2010) Curcumin therapeutic promises and bioavailability in colorectal cancer. Drugs Today 46(7):523CrossRefPubMedGoogle Scholar
  37. 37.
    Shtutman M, Zhurinsky J, Simcha I, Albanese C, D’Amico M, Pestell R, Ben-Ze’ev A (1999) The cyclin D1 gene is a target of the β-catenin/LEF-1 pathway. Proc Natl Acad Sci 96(10):5522–5527CrossRefPubMedGoogle Scholar
  38. 38.
    Sun S-C (2011) Non-canonical NF-κB signaling pathway. Cell Res 21(1):71–85CrossRefGoogle Scholar
  39. 39.
    Ting C-T, Li W-C, Chen C-Y, Tsai T-H (2015) Preventive and therapeutic role of traditional Chinese herbal medicine in hepatocellular carcinoma. J Chin Med Assoc 78(3):139–144CrossRefPubMedGoogle Scholar
  40. 40.
    Tønnesen HH, Karlsen J (1985) Studies on curcumin and curcuminoids. Z Lebensm Unters Forsch 180(5):402–404CrossRefPubMedGoogle Scholar
  41. 41.
    Wahlström B, Blennow G (1978) A study on the fate of curcumin in the rat. Basic Clin Pharmacol Toxicol 43(2):86–92Google Scholar
  42. 42.
    Wang T, Wang Y, Wu M-C, Guan X-Y, Yin Z-F (2004) Activating mechanism of transcriptor NF-kappaB regulated by hepatitis B virus X protein in hepatocellular carcinoma. World J Gastroenterol 10(3):356–360CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Wang Y-J, Pan M-H, Cheng A-L, Lin L-I, Ho Y-S, Hsieh C-Y, Lin J-K (1997) Stability of curcumin in buffer solutions and characterization of its degradation products. J Pharm Biomed Anal 15(12):1867–1876CrossRefPubMedGoogle Scholar
  44. 44.
    Yallapu MM, Jaggi M, Chauhan SC (2012) Curcumin nanoformulations: a future nanomedicine for cancer. Drug Discov Today 17(1):71–80CrossRefPubMedGoogle Scholar
  45. 45.
    Yamamoto Y, Gaynor RB (2001) Therapeutic potential of inhibition of the NF-κB pathway in the treatment of inflammation and cancer. J Clin Invest 107(2):135–142CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Zheng R, Deng Q, Liu Y, Zhao P (2017) Curcumin inhibits gastric carcinoma cell growth and induces apoptosis by suppressing the Wnt/β-catenin signaling pathway. Med Sci Monit 23:163–171CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Zhou M, Li Z, Han Z, Tian N (2015) Paclitaxel-sensitization enhanced by curcumin involves down-regulation of nuclear factor-κ B and Lin28 in Hep3B cells. J Recept Sig Transduct 35(6):618–625CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd 2017

Authors and Affiliations

  • Saipriya Lammata
    • 1
  • Mundla Srilatha
    • 2
  • Ganji Purnachandra Nagaraju
    • 3
  1. 1.Rice UniversityHoustonUSA
  2. 2.Department of BiotechnologySri Venkateswara UniversityTirupatiIndia
  3. 3.Department of Hematology and Medical Oncology, Winship Cancer InstituteEmory UniversityAtlantaUSA

Personalised recommendations

Cite chapter

Buy options