Volume 22, Issue 4 (2019)                   mjms 2019, 22(4): 211-220 | Back to browse issues page

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Roozbehi S, Dadashzadeh S, Sajedi R. Promoting the Effects of Curcumin Toxicity on Different Cancer Cell Lines by Developing the β-Cyclodextrin-Curcumin Inclusion Complex. mjms. 2019; 22 (4) :211-220
URL: http://mjms.modares.ac.ir/article-30-40041-en.html
1- Biochemistry Department, Biological Sciences Faculty, Tarbiat Modares University, Tehran, Iran
2- Department of Pharmaceutics & Nanotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3- Biochemistry Department, Biological Sciences Faculty, Tarbiat Modares University, Tehran, Iran , sajedi_r@modares.ac.ir
Abstract:   (15115 Views)
Aims: Curcumin (CUR) is a hydrophobic polyphenol compound and possesses a wide range of biological applications including cancer therapy. However, its prominent application in cancer treatment is limited due to poor solubility and bioavailability. Cyclodextrins (CDs) as natural nanocapsules are comprised of glucose units. One of the characteristics of them is to create complex with hydrophobic guest molecules in nanopores. In the current study, in order to improve the solubility, bioavailability, and efficacy of CUR, β-cyclodextrin-curcumin (β-CD-CUR) inclusion complexes were prepared and its effect on cancer and normal cells was examined.
Materials & Methods: In this study, first, β-CD-CUR complexes were prepared using freeze-drying method and the formation of these complexes was characterized by fluorescence spectroscopy. The encapsulation efficiency of CUR in β-CD was calculated for each concentration. After investigating the release of CUR from β-CD at different temperatures, the therapeutic effects of β-CD-CUR inclusion complexes for cancer and normal cell lines were evaluated by MTT assay.
Findings: The CUR encapsulation efficiency in β-CD was 33.92±1.32%. Fluorescence spectroscopic studies confirmed the formation of stable inclusion complex. The results also showed that CUR release from β-CD was higher in thermal conditions of cancer cells (42°C) than in normal cells and ambient temperatures. The results of MTT assay depicted that encapsulated CUR in β-CD has a significant inhibitory effect on proliferation of cancer cells compared to free CUR.
Conclusion: The results provided acceptable evidence for cell proliferation inhibition of β-CD-CUR complexes on cancer cells. There were no adverse effects detected for normal cells.
Full-Text [PDF 1184 kb]   (663 Downloads)    
Article Type: Original Research | Subject: Cell Therapy
Received: 2020/01/20 | Accepted: 2020/05/10

1. Lee KW, Bode AM, Dong Z. Molecular targets of phytochemicals for cancer prevention. Nat Rev Cancer. 2011;11(3):211-8. [Link] [DOI:10.1038/nrc3017]
2. Early Breast Cancer Trialists' Collaborative Group. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: An overview of the randomised trials. Lancet. 2005;365(9472):1687-717. [Link] [DOI:10.1016/S0140-6736(05)66544-0]
3. Allen TM. Ligand-targeted therapeutics in anticancer therapy. Nat Rev Cancer. 2002;2(10):750-63. [Link] [DOI:10.1038/nrc903]
4. Wanchai A, Armer JM, Stewart BR. Complementary and alternative medicine use among women with breast cancer: A systematic review. Clin J Oncol Nurs. 2010;14(4):E45-55. [Link] [DOI:10.1188/10.CJON.E45-E55]
5. Lai JN, Wu CT, Wang JD. Prescription pattern of Chinese herbal products for breast cancer in Taiwan: A population-based study. Evid Based Complement Altern Med. 2012;2012:891893. [Link] [DOI:10.1155/2012/891893]
6. Aziz K, Nowsheen S, Georgakilas A. Nanotechnology in cancer therapy: Targeting the inhibition of key DNA repair pathways. Curr Mol Med. 2010;10(7):626-39. [Link] [DOI:10.2174/156652410792630599]
7. Bharali DJ, Siddiqui IA, Adhami VM, Chamcheu JC, Aldahmash AM, Mukhtar H, et al. Nanoparticle delivery of natural products in the prevention and treatment of cancers: Current status and future prospects. Cancers. 2011;3(4):4024-45. [Link] [DOI:10.3390/cancers3044024]
8. Liu D, Chen Z. The effect of curcumin on breast cancer cells. J Breast Cancer. 2013;16(2):133-7. [Link] [DOI:10.4048/jbc.2013.16.2.133]
9. Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as "Curecumin": From kitchen to clinic. Biochem Pharmacol. 2008;75(4):787-809. [Link] [DOI:10.1016/j.bcp.2007.08.016]
10. Aggarwal BB, Sung B. Pharmacological basis for the role of curcumin in chronic diseases: An age-old spice with modern targets. Trends Pharmacol Sci. 2009;30(2):85-94. [Link] [DOI:10.1016/j.tips.2008.11.002]
11. Kunnumakkara AB, Anand P, Aggarwal BB. Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins. Cancer Lett. 2008;269(2):199-225. [Link] [DOI:10.1016/j.canlet.2008.03.009]
12. Sun M, Su X, Ding B, He X, Liu X, Yu A, et al. Advances in nanotechnology-based delivery systems for curcumin. Nanomedicine. 2012;7(7):1085-100. [Link] [DOI:10.2217/nnm.12.80]
13. Anand P, Sundaram Ch, Jhurani S, Kunnumakkara AB, Aggarwal BB. Curcumin and cancer: An "old-age" disease with an "age-old" solution. Cancer Lett. 2008;267(1):133-64. [Link] [DOI:10.1016/j.canlet.2008.03.025]
14. Saraswathy M, Gong Sh. Different strategies to overcome multidrug resistance in cancer. Biotechnol Adv. 2013;31(8):1397-407. [Link] [DOI:10.1016/j.biotechadv.2013.06.004]
15. Naksuriya O, Okonogi S, Schiffelers RM, Hennink WE. Curcumin nanoformulations: A review of pharmaceutical properties and preclinical studies and clinical data related to cancer treatment. Biomaterials. 2014;35(10):3365-83. [Link] [DOI:10.1016/j.biomaterials.2013.12.090]
16. Baglole KN, Boland PG, Wagner BD. Fluorescence enhancement of curcumin upon inclusion into parent and modified cyclodextrins. J Photochem Photobiol A Chem. 2005;173(3):230-7. [Link] [DOI:10.1016/j.jphotochem.2005.04.002]
17. Messner M, Kurkov SV, Jansook P, Loftsson T. Self-assembled cyclodextrin aggregates and nanoparticles. Int J Pharm. 2010;387(1-2):199-208. [Link] [DOI:10.1016/j.ijpharm.2009.11.035]
18. Del Valle EM. Cyclodextrins and their uses: A review. Process biochemistry. 2004;39(9):1033-46. [Link] [DOI:10.1016/S0032-9592(03)00258-9]
19. Barone G, Castronuovo G, Di Ruocco V, Elia V, Giancola C. Inclusion compounds in water: Thermodynamics of the interaction of cyclomaltohexaose with amino acids at 25°. Carbohydr Res. 1989;192:331-41. [Link] [DOI:10.1016/0008-6215(89)85191-2]
20. Bertolla C, Rolin S, Evrard B, Pochet L, Masereel B. Synthesis and pharmacological evaluation of a new targeted drug carrier system: β-Cyclodextrin coupled to oxytocin. Bioorg Med Chem Lett. 2008;18(6):1855-8. [Link] [DOI:10.1016/j.bmcl.2008.02.017]
21. Evrard B, Bertholet P, Guéders M, Flament MP, Piel G, Delattre L, et al. Cyclodextrins as a potential carrier in drug nebulization. J Controll Release. 2004;96(3):403-10. [Link] [DOI:10.1016/j.jconrel.2004.02.010]
22. Challa R, Ahuja A, Ali J, Khar RK. Cyclodextrins in drug delivery: An updated review. AAPS PharmSciTech. 2005;6(2):E329-57. [Link] [DOI:10.1208/pt060243]
23. Yallapu MM, Jaggi M, Chauhan SC. β-Cyclodextrin-curcumin self-assembly enhances curcumin delivery in prostate cancer cells. Colloids Surf B Biointerfaces. 2010;79(1):113-25. [Link] [DOI:10.1016/j.colsurfb.2010.03.039]
24. Sieuwerts AM, Klijn JG, Peters HA, Foekens JA. The MTT tetrazolium salt assay scrutinized: How to use this assay reliably to measure metabolie activity of cell cultures in vitro for the assessment of growth characteristics, IC50-values and cell survival. Clin Chem Lab Med. 1995;33(11):813-24. [Link] [DOI:10.1515/cclm.1995.33.11.813]
25. Hoshino M, Imamura M, Ikehara K, Hama Y. Fluorescence enhancement of benzene derivatives by forming inclusion complexes with. beta.-cyclodextrin in aqueous solutions. J Phys Chem. 1981;85(13):1820-3. [Link] [DOI:10.1021/j150613a012]
26. Bisht S, Feldmann G, Soni Sh, Ravi R, Karikar C, Maitra A, et al. Polymeric nanoparticle-encapsulated curcumin ("nanocurcumin"): A novel strategy for human cancer therapy. J Nanobiotechnol. 2007;5(1):3. [Link] [DOI:10.1186/1477-3155-5-3]
27. Al-Hassan KA, Klein UK, Suwaiyan A. Normal and twisted intramolecular charge-transfer fluorescence of 4-dimethylaminobenzonitrile in α-cyclodextrine cavities. Chem Phys Lett. 1993;212(6):581-7. [Link] [DOI:10.1016/0009-2614(93)85489-B]
28. Liu K, Liu PC, Liu R, Wu X. Dual AO/EB staining to detect apoptosis in osteosarcoma cells compared with flow cytometry. Med Sci Monit Basic Res. 2015;21:15-20. [Link] [DOI:10.12659/MSMBR.893327]
29. Manzoori JL, Abdolmohammad-Zadeh H, Amjadi M. Study on the inclusion complex between β-cyclodextrin and celecoxib by spectrofluorimetry and its analytical application. Il Farmaco. 2005;60(6-7):575-81. [Link] [DOI:10.1016/j.farmac.2005.02.003]
30. Shaikh J, Ankola DD, Beniwal V, Singh D, Kumar MR. Nanoparticle encapsulation improves oral bioavailability of curcumin by at least 9-fold when compared to curcumin administered with piperine as absorption enhancer. Eur J Pharm Sci. 2009;37(3-4):223-30. [Link] [DOI:10.1016/j.ejps.2009.02.019]
31. Chirio D, Gallarate M, Trotta M, Carlotti ME, Gaudino EC, Cravotto G. Influence of α-and γ-cyclodextrin lipophilic derivatives on curcumin-loaded SLN. J Incl Phenom Macrocycl Chem. 2009;65(3-4):391. [Link] [DOI:10.1007/s10847-009-9597-7]
32. Vikas Y, Sandeep K, Braham D, Manjusha Ch, Budhwar V. Cyclodextrin complexes: An approach to improve the physicochemical properties of drugs and applications of cyclodextrin complexes. Asian J Pharm. 2018;12(2):394-409. [Link]
33. Xu D, Wang L, Gourevich D, Kabha E, Arditti F, Athamna M, et al. Synthesis and inclusion study of a novel γ-cyclodextrin derivative as a potential thermo-sensitive carrier for doxorubicin. Chem Pharm Bull. 2014;62(7):627-35. [Link] [DOI:10.1248/cpb.c13-00950]
34. Topuz F, Uyar T. Electrospinning of cyclodextrin functional nanofibers for drug delivery applications. Pharmaceutics. 2019;11(1):6. [Link] [DOI:10.3390/pharmaceutics11010006]
35. Al Omari MM, Zughul MB, Davies JE, Badwan AA. Effect of buffer species on the complexation of basic drug terfenadine with β-cyclodextrin. J Incl Phenom Macrocycl Chem. 2007;58(3-4):227-35. [Link] [DOI:10.1007/s10847-006-9147-5]
36. Alexis F, Pridgen E, Molnar LK, Farokhzad OC. Factors affecting the clearance and biodistribution of polymeric nanoparticles. Mol Pharm. 2008;5(4):505-15. [Link] [DOI:10.1021/mp800051m]
37. Dahan A, Miller JM, Hoffman A, Amidon GE, Amidon GL. The solubility-permeability interplay in using cyclodextrins as pharmaceutical solubilizers: Mechanistic modeling and application to progesterone. J Pharm Sci. 2010;99(6):2739-49. [Link] [DOI:10.1002/jps.22033]
38. Chen J, Qin X, Zhong S, Chen S, Su W, Liu Y. Characterization of curcumin/cyclodextrin polymer inclusion complex and investigation on its antioxidant and antiproliferative activities. Molecules. 2018;23(5):1179. [Link] [DOI:10.3390/molecules23051179]
39. Wilken R, Veena MS, Wang MB, Srivatsan ES. Curcumin: A review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma. Mol Cancer. 2011;10(1):12. [Link] [DOI:10.1186/1476-4598-10-12]
40. Ravindran J, Prasad S, Aggarwal BB. Curcumin and cancer cells: How many ways can curry kill tumor cells selectively?. AAPS J. 2009;11(3):495-510. [Link] [DOI:10.1208/s12248-009-9128-x]
41. Syng-ai Ch, Kumari AL, Khar A. Effect of curcumin on normal and tumor cells: Role of glutathione and bcl-2. Mol Cancer Ther. 2004;3(9):1101-8. [Link]

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