Comparative evaluation of curcumin and curcumin loaded- dendrosome nanoparticle effects on the viability of SW480 colon carcinoma and Huh7 hepatoma cells

Document Type: Original paper


1 Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.

2 Department of Microbiology, Faculty of Basic Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran.

3 Department of Genetics, Faculty of Basic Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran.

4 Department of Biology, Faculty of Modern Sciences, Medical Branch of Tehran Islamic Azad University, Tehran, Iran.

5 Department of Medical Biotechnology, Tabriz University of Medical Science, Tabriz, Iran.

6 Department of Biology, Faculty of Basic Sciences, East Tehran Branch, Islamic Azad University, Tehran, Iran.


Background and objectives: Colorectal cancer is the third most common cancer and a major cause of morbidity globally. Hepatocellular carcinoma is a leading cause of death in the world. About 80% of all anticancer drugs are somehow related to natural products. One of the most important of these natural compounds is curcumin, the main component of turmeric that has a wide range of pharmacological activities. Curcumin has been found to suppress cell proliferation and decrease cell viability in various types of cancer cells; however, owing to lack of aqueous solubility, curcumin has shown reduced bioavailability in studies. Recent studies have shown that new 400th generation of dendrosome nanoparticle can increase bioavailability of curcumin and thus enhance the cytotoxic properties.  The aim of this study was to determine effectiveness of curcumin alone and in combination with 400th generation dendrosome nanoparticles (DNC) on cell viability rate in SW480 and Huh7 cells. Methods: SW480 and Huh7 cells were incubated with different concentrations of curcumin and DNC (0-50μM) for 24, 48 and 72 h. Then cytotoxicity was assessed by MTT assay and IC50 was determined. Results: The results suggested that the concentration-dependent inhibitory effect of DNC was stronger than curcumin on SW480 and Huh7 cells. Conclusion: The results suggest DNC as a more effective herbal anticancer agent for colorectal and hepatocellular tumors.


[1]  Goldberg RM, Sargent DJ, Morton RF, Fuchs CS, Ramanathan RK, Williamson SK, Findlay BP, Pitot HC, Alberts SR. A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol. 2004; 22(1): 23-30.

[2]  Jemal A. Cancer statistics. CA Cancer J Clin. 2009; 59(4): 225-249.

[3]  Giovannucci E. Diet, body weight, and colorectal cancer: a summary of the epidemiologic evidence. J Womens Health (Larchmt). 2003; 12(2): 173-182.

[4]  Ikeda K, Saitoh S, Koida I, Arase Y, Tsubota A, Chayama K, Kumada H, Kawanishi M. A multivariate analysis of risk factors for hepatocellular carcinogenesis: A prospective observation of 795 patients with viral and alcoholic cirrhosis. Hepatology. 1993; 18(1): 47-53.

[5]  Namiki M. Antioxidants/antimutagens in food. Crc Cr Rev Food Sci. 1990; 29(4): 273-300.

[6]  Clarkson PM, Thompson HS. Antioxidants: what role do they play in physical activity and health. Am J Clin Nutr. 2000; 72(2): 637-646.

[7]  Ghasemian A, Mehrabian S, Majd A. Peel extracts of two Iranian cultivars of pomegranate (Punica granatum) have antioxidant and antimutagenic activities. Pak J Biol Sci. 2006; 9(7): 1402-1405.

[8]  Sporn MB. The War on Cancer: A Review. Ann Ny Acad Sci. 1997; 833: 137-146.

[9]  Kuo ML, Huang TS, Lin JK. Curcumin, an antioxidant and anti-tumor promoter, induces apoptosis in human leukemia cells. Biochim Biophys Acta. 1996; 1317(2): 95-100.

[10]  Ammon HP, Wahl MA. Pharmacology of Curcuma longa. Planta Med. 1991; 57(1): 1-7.

[11]  Khor TO, Keum YS, Lin W, Kim JH, Hu R, Shen G, Xu C, Gopalakrishnan A, Reddy B, Zheng X, Conney AH, Kong AN. Combined inhibitory effects of curcumin and phenethyl isothiocyanate on the growth of human PC-3 prostate xenografts in immunodeficient mice. Cancer Res. 2006; 66(2): 613-621.

[12]  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.

[13]  Das T, Sa G, Saha B, Das K. Multifocal signal modulation therapy of cancer: ancient weapon, modern targets. Mol Cell Biochem. 2010; 336(1-2): 85-95.

[14]  Mehta K, Pantazis P, McQueen T, Aggarwal BB. Antiproliferative effect of curcumin (diferuloylmethane) against human breast tumor cell lines. Anticancer Drugs. 1997; 8(5): 470-481.

[15]  Radhakrishna Pillai GSA, Hassanein TI, Chauhan DP, Carrier E. Induction of apoptosis in human lung cancer cells by curcumin. Cancer Lett. 2004; 208(2): 163‑170.

[16]  Rashmi R, Kumar S, Karunagaran D. Ectopic expression      of Bcl-XL or Ku70 protects human colon cancer cells (SW480) against curcumin-induced apoptosis while their down-regulation potentiates it. Carcinogenesis. 2004; 25(10): 1867-1877.

[17]  Johnson JJ, Mukhtar H. Curcumin for chemoprevention of colon cancer. Cancer Lett. 2007; 255(2): 170-181.

[18]  Kim K, Kim KH, Kim HY, Cho HK, Sakamoto N, Cheong J. Curcumin inhibits hepatitis C virus replication via suppressing the Akt-SREBP-1 pathway. Febs Letters. 2010; 584(4): 707-712.

[19]  Anand P, Nair HB, Sung B, Kunnumakkara AB, Yadav VR, Tekmal RR, Aggarwal BB. Design of curcumin-loaded PLGA nanoparticles formulation with enhanced cellular uptake, and increased bioactivity in vitro and superior bioavailability in vivo. Biochem Pharmacol. 2010; 79(3): 330-338.

[20]  Kim HJ, Park SY, Park OJ, Kim YM. Curcumin suppresses migration and proliferation of Hep3B hepatocarcinoma cells through inhibition of the Wnt signaling pathway. Mol Med Rep. 2013; 8(1): 282-286.

[21]  Babaei E, Sadeghizadeh M, Hassan ZM, Feizi MAH, Najafi F, Hashemi SM. Dendrosomal curcumin significantly suppresses cancer cell proliferation in vitro and in vivo. Int Immunopharmacol. 2012; 12(1): 226-234.

[22]  Sadeghizadeh M, Ranjbar B, Damaghi M, Khaki L, Sarbolouki MN, Najafi F. Dendrosomes as novel gene porters-III. J Chemi Technol Biotechnol. 2008; 83(6): 912-920.

[23]  Sarbolouki MN, Sadeghizadeh M, Yaghoobi MM, Karami A, Lohrasbi T. Dendrosomes: a novel family of vehicles for transfection and therapy. J Chem Technol Biotechnol. 2000; 75(10): 919-922.

[24]  Tahmasebi Mirgani M, Isacchi B, Sadeghizadeh M, Marra F, Bilia AR, Mowla SJ, Najafi F, Babaei E. Dendrosomal-curcumin nano formulation downregulates pluripotency genes via miR-145 activation in U87MG glioblastoma cells.Int J Nanomed. 2013; 9: 403-417.

[25]  Gou M, Men K, Shi H, Xiang M, Zhang J, Song J, Long J, Wan Y, Luo F, Zhao X, Qian Z. Curcumin-loaded biodegradable polymeric micelles for colon cancer therapy in vitro and in vivo. Nanoscale. 2011; 3(4): 1558-1567.

[26]  Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983; 65(1-2): 55-63.

[27]  Sebaugh JL. Guidelines for accurate EC50/IC50 estimation. Pharm Stat. 2011; 10(2): 128-134.

[28]  Kimelman D, Xu W. Beta-catenin destruction complex: insights and questions from a structural perspective. Oncogene. 2006; 25(57): 7482-7491.

[29]  Chen HW, Lee JY, Huang JY, Wang CC, Chen WJ, Su SF, Huang CW, Ho CC, Chen JJ, Tsai MF, Yu SL, Yang PC. Curcumin inhibits lung cancer cell invasion and metastasis through the tumor suppressor HLJ1. Cancer Res. 2008; 68(18): 7428-7438.

[30]  Yu W, Xu YC, Tao Y, He P, Li Y, Wu T, Zhu YP, Li J, Wu JX, Dai J. DcR3 regulates the growth and metastatic potential of SW480 colon cancer cells. Oncol Rep. 2013; 30(6): 2741-2748.

[31]  Bharat BA, Shishir S, Yasunari T. Curcumin suppresses the paclitaxel-induced nuclear factor metastasis of human breast cancer in nude mice kb pathway in breast cancer cells and inhibits lung. Clin cancer Res. 2005; 11(20): 7490-7498.

[32]  Aggarwal S, Ichikawa H, Takada Y, Sandur SK, Shishodia S, Aggarwal BB. Curcumin (diferuloylmethane) down-regulates expression of cell proliferation and antiapoptotic and metastatic gene products through suppression of IkappaBalpha kinase and Akt activation. Mol Pharmacol. 2006; 69(1): 195-206.

[33]  Hong JH, Ahn KS, Bae E, Jeon SS, Choi HY. The effects of curcumin on the invasiveness of prostate cancer in vitro and in vivo. Prostate Cancer Prostatic Dis. 2006; 9(2): 147-152.

[34]  Su CC, Lin JG, Li TM, Chung JG, Yang JS, Ip SW, Lin WC, Chen GW. Curcumin. induced apoptosis of human colon cancer Colo 205 cells through the production of ROS, Ca2+and the activation of caspase-3. Anticancer Res. 2006; 26(6B): 4379-4389.

[35]  Wang X, Wang Q, Ives KL, Evers BM. Curcumin Inhibits neurotensin-mediated interleukin-8 production and migration of HCT116 human colon cancer cells. Clin Cancer Res. 2006; 12(18): 5346-5355.

[36]  Lin YG, Kunnumakkara AB, Nair A, Merritt WM, Han LY, Armaiz-Pena GN, Kamat AA, Spannuth WA, Gershenson DM, Lutgendorf SK, Aggarwal BB, Sood AK.Curcumin inhibits tumor growth and angiogenesis in ovarian carcinoma by targeting the nuclear factor-kappaB pathway. Clin Cancer Res. 2007; 13(11): 3423-3430.

[37]  Kim HI, Huang H, Cheepala S, Huang S, Chung J. Curcumin inhibition of integrin (alpha6beta4)-dependent breast cancer cell motility and invasion. Cancer Prev Res. 2008; 1(5): 385-391.

[38]  Cai XZ, Wang J, Li XD, Wang GL, Liu FN, Cheng MS, Li F. Curcumin suppresses proliferation and invasion in human gastric cancer cells by downregulation of PAK1 activity and cyclin D1 expression. Cancer Biol Ther. 2009; 8(14): 1360-1368.

[39]  Herman JG, Stadelman HL, Roselli CE. Curcumin blocks CCL2 induced adhesion, motility and invasion, in part, through down-regulation of CCL2 expression and proteolytic activity. Int J Oncol. 2009; 34(5): 1319-1327.

[40]  Bangaru ML, Chen S, Woodliff J, Kansra S. Curcumin (diferuloylmethane) induces apoptosis and blocks migration of human medulloblastoma cells. Anticancer Res. 2010; 30(2): 499-504.

[41]  Ibrahim A, El-Meligy A, Fetaih H, Dessouki A, Stoica G, Barhoumi R. Effect of curcumin and meriva on the lung metastasis of murine mammary gland adenocarcinoma. In Vivo. 2010; 24(4): 401-408.

[42]  Mudduluru G, George-William JN, Muppala S, Asangani IA, Kumarswamy R, Nelson LD, Allgayer H. Curcumin regulates miR-21 expression and inhibits invasion and metastasis in colorectal cancer. Bioscience Rep. 2011; 31(3): 185-197.

[43]  Collett GP, Campbell FC. Curcumin induces c-jun N-terminal kinase-dependent apoptosis in HCT116 human colon cancer cells. Carcinogenesis. 2004; 25(11): 2183-2189.

[44]  Notarbartolo M, Poma P, Perri D, Dusonchet L, Cervello M, D'Alessandro N. 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-kB activation levels and in IAP gene expression. Cancer Lett. 2005; 224(1): 53-65.