subscribe: Posts | Comments | Email

The antiproliferative and anticancerogenic effects of nano-curcumin in rat colon cancer

Comments Off

Original Article

Tehran Univ Med J (TUMJ) 2013 August;71(5):277-84

Author Affiliations:
Mahmood Khaniki M.D.1
Saleh Azizian M.D.1
Ali Mohammad Alizadeh Ph.D.2*
Hamidreza Hemmati M.Sc.2
Nabbi Emamipour M.Sc.3
Mohammad Ali Mohagheghi M.D.2

1- Department of Pathology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
2- Cancer Research Center, Tehran University of Medical Sciences, Tehran, Iran.
3- Department of Biotechnology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

* Corresponding author: Keshavarz Blvd., Cancer Research Center, Cancer Institute of Iran, Tehran, Iran.
Tel: +98-21-61192501
E-mail: aalizadeh@razi.tums.ac.ir

Received: March 15, 2013    Accepted: May 01, 2013

Abstract:
Background: Curcumin, the active ingredient of turmeric, has the ability to inhibit the carcinogenic pathways, and thus can prevent or postpone the carcinogenic process in different animal species. Retention time of curcumin is short due to the quick excretion of the body, so, the therapeutic effects of curcumin are restricted resulting in short-term retention in the plasma. Therefore, several methods are used for increasing the efficien-cy of curcumin in plasma and tissues. The present study is designed to evaluate the effects of the anti-proliferative and anti-carcinogenic of nano-curcumin in rat colon cancer.

Methods: In this study which was performed in Cancer Research Center of Tehran University of Medical Sciences in 2012. Thirty rats have divided into control, curcumin and nano-curcumin groups. All animals received azoxymethane (15 mg/kg, s.c) as a carcinogen, once a week for two consecutive weeks. Animals received curcumin 0.2% and nano-curcumin 2 weeks before azoxymethane injection up to 14 weeks after the last injection of azoxymethane in curcumin and nano-curcumin groups, respectively. At the end of experiment, the colorectal specimens from all mucosal lesions were obtained for histo-and-immunohistochemical (Ki-67 and COX-2) studies.

Results: The cytological and morphological changes of the cells in nano-curcumin group were significantly lower compared to other groups (P<0.05). In addition, the Ki-67 and COX-2 proteins expression was lower in the nano-curcumin group in compare-son with the curcumin and control groups (P<0.05).

Conclusion: The results indicate that the using a suitable nanoparticle can be appropria-tely resolved the low bioavailability of curcumin. This can be an important method to use of natural products in the prevention and/or treatment of cancer.

Keywords: Colon cancer, COX-2, curcumin, rat.




  1. Jemal A, Center MM, DeSantis C, Ward EM. Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomarkers Prev 2010;19(8):1893-907.
  2. Mahmoodi M, Alizadeh AM, Sohanaki H, Rezaei N, Amini-Najafi F, Khosravi AR, et al. Impact of fumonisin b1 on the production of inflammatory cytokines by gastric and colon cell lines. Iran J Aller-gy Asthma Immunol 2012;11(2):165-73.
  3. Alizadeh AM, Rohandel G, Roudbarmohammadi S, Roudbary M, Sohanaki H, Ghiasian SA, et al. Fumonisin B1 contamination of cereals and risk of esophageal cancer in a high risk area in nor-theastern Iran. Asian Pac J Cancer Prev 2012;13(6):2625-8.
  4. Aggarwal BB, Shishodia S. Molecular targets of dietary agents for prevention and therapy of cancer. Biochem Pharmacol 2006;71: 1397-421.
  5. Lin JK. Molecular targets of curcumin. Adv Exp Med Biol 2007;595 :227-43.
  6. Varalakshmi Ch, Ali AM, Pardhasaradhi BV, Srivastava RM, Singh S, Khar A. Immunomodulatory effects of curcumin: In-vivo. Int Immunopharmacol 2008;8(5):688-700.
  7. Yang KY, Lin LC, Tseng TY, Wang SC, Tsai TH. Oral bioavailabi-lity of curcumin in rat and the herbal analysis from Curcuma longa by LC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci 2007;853(1-2):183-9.
  8. Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS. Influence of piperine on the pharmacokinetics of curcumin in anim-als and human volunteers. Planta Med 1998;64(4):353-6.
  9. Yogosawa S, Yamada Y, Yasuda S, Sun Q, Takizawa K, Sakai T. Dehydrozingerone, a structural analogue of curcumin, induces cell-cycle arrest at the G2/M phase and accumulates intracellular ROS in HT-29 human colon cancer cells. J Nat Prod 2012;75(12):2088-93.
  10. Helson L, Bolger G, Majeed M, Vcelar B, Pucaj K, Matabudul D. Infusion pharmacokinetics of Lipocurc™ (liposomal curcumin) and its metabolite tetrahydrocurcumin in Beagle dogs. Anticancer Res 2012;32(10):4365-70.
  11. Alizadeh AM, Khaniki M, Azizian S, Mohaghgheghi MA, Sadeghizadeh M, Najafi F. Chemoprevention of azoxymethane-initiated colon cancer in rat by using a novel polymeric nanocarrier-curcumin. Eur J Pharmacol 2012;689(1-3):226-32.
  12. Ledley FD. Nonviral gene therapy: the promise of genes as pharma-ceutical products. Hum Gene Ther 1995;6(9):1129-44.
  13. Sarbolouki MN, Sadeghizadeh M, Yaghoobi MM, Karami A, Lohrasbi T. Dendrosomes: a novel family of vehicles for transfec-tion and therapy. J Chem Technol Biotechnol 2000;75(10):919-22.
  14. Pourasgari F, Ahmadian S, Salmanian AH, Sarbolouki MN, Massumi M. Low cytotoxicity effect of dendrosome as an efficient carrier for rotavirus VP2 gene transferring into a human lung cell line: dendrosome, as a novel intranasally gene porter. Mol Biol Rep 2009;36(1):105-9.
  15. Sarbolouki MN, Alizadeh AM, Khaniki M, Azizian S, Mohagheghi MA. Protective effect of dendrosomal curcumin combination on colon cancer in rat. Tehran Univ Med J (TUMJ) 2012;69(11):678-85.
  16. Babaei E, Sadeghizadeh M, Hassan ZM, Feizi MA, Najafi F, Hashemi SM. Dendrosomal curcumin significantly suppresses can-cer cell proliferation in vitro and in vivo. Int Immunopharmacol 2012;12(1):226-34.
  17. Takahashi M, Mutoh M, Kawamori T, Sugimura T, Wakabayashi K. Altered expression of beta-catenin, inducible nitric oxide syn-thase and cyclooxygenase-2 in azoxymethane-induced rat colon carcinogenesis. Carcinogenesis 2000;21(7):1319-27.
  18. Allred DC, Harvey JM, Berardo M, Clark GM. Prognostic and predictive factors in breast cancer by immunohistochemical analy-sis. Mod Pathol 1998;11:155-68.
  19. Gerdes J, Lemke H, Baisch H, Wacker HH, Schwab U, Stein H. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 1984 ;133(4):1710-5.
  20. Shishodia S, Chaturvedi MM, Aggarwal BB. Role of curcumin in cancer therapy. Curr Probl Cancer 2007;31(4):243-305.
  21. Mukhopadhyay A, Banerjee S, Stafford LJ, Xia C, Liu M, Aggarwal BB. Curcumin-induced suppression of cell proliferation correlates with down-regulation of cyclin D1 expression and CDK4-mediated retinoblastoma protein phosphorylation. Oncogene 2002;21(57):8852-61.
  22. Bharti AC, Donato N, Singh S, Aggarwal BB. Curcumin (diferulo-ylmethane) down-regulates the constitutive activation of nuclear factor-kappa B and IkappaBalpha kinase in human multiple myel-oma cells, leading to suppression of proliferation and induction of apoptosis. Blood 2003;101(3):1053-62.
  23. Hla T, Neilson K. Human cyclooxygenase-2 cDNA. Proc Natl Acad Sci USA 1992;89(16):7384-8.
  24. Stratton MS, Alberts DS. Current application of selective COX-2 inhibitors in cancer prevention and treatment. Oncology (Williston Park) 2002;16(5 Suppl 4):37-51.
  25. Subbaramaiah K, Morris PG, Zhou XK, Morrow M, Du B, Giri D, et al. Increased levels of COX-2 and prostaglandin E2 contribute to elevated aromatase expression in inflamed breast tissue of obese women. Cancer Discov 2012;2(4):356-65.
  26. Bengmark S. Curcumin, an atoxic antioxidant and natural NFka-ppaB, cyclooxygenase-2, lipooxygenase, and inducible nitric oxide synthase inhibitor: a shield against acute and chronic diseases. JPEN J Parenter Enteral Nutr 2006;30(1):45-51.
  27. Sharma RA, Gescher AJ, Steward WP. Curcumin: the story so far. Eur J Cancer 2005;41(13):1955-68.
  28. Sadeghizadeh M, Ranjbar B, Damaghi M, Khaki L, Sarbolouki MN, Najafi F, et al. Dendrosomes as novel gene porters-III. J Chem Technol Biotechnol 2008;83(6):912-20.


This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

TUMJ Tools:

Comments are closed.