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http://dx.doi.org/10.7314/APJCP.2015.16.9.3917

Dendrosomal Curcumin Suppresses Metastatic Breast Cancer in Mice by Changing M1/M2 Macrophage Balance in the Tumor Microenvironment  

Shiri, Sadaf (Immunology Research Center, Tehran University of Medical Sciences)
Alizadeh, Ali Mohammad (Cancer Research Center, Tehran University of Medical Sciences)
Baradaran, Behzad (Immunology Research Center, Tehran University of Medical Sciences)
Farhanghi, Baharak (Cancer Research Center, Tehran University of Medical Sciences)
Shanehbandi, Dariush (Immunology Research Center, Tehran University of Medical Sciences)
Khodayari, Saeed (Cancer Research Center, Tehran University of Medical Sciences)
Khodayari, Hamid (Cancer Research Center, Tehran University of Medical Sciences)
Tavassoli, Abbas (Department of Pathology, Faculty of Veterinary Medicine, Tehran University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.16, no.9, 2015 , pp. 3917-3922 More about this Journal
Abstract
Curcumin, a lipid-soluble compound extracted from the plant Curcuma Longa, has been found to exert immunomodulatory effects via macrophages. However, most studies focus on the low bioavailability issue of curcumin by nano and microparticles, and thus the role of macrophages in the anticancer mechanism of curcumin has received little attention so far. We have previously shown the potential biocompatibility, biodegradability and anti-cancer effects of dendrosomal curcumin (DNC). In this study, twenty-seven BALB/c mice were equally divided into control as well as 40 and 80 mg/kg groups of DNC to investigate the involvement of macrophages in the antitumor effects of curcumin in a typical animal model of metastatic breast cancer. At the end of intervention, the tumor volume and weight were significantly reduced in DNC groups compared to control (P<0.05). Histopathological data showed the presence of macrophages in tumor and spleen tissues. Real-time PCR results showed that DNC increased the expression of STAT4 and IL-12 genes in tumor and spleen tissues in comparison with control (P<0.05), referring to the high levels of M1 macrophages. Furthermore treatment with DNC decreased STAT3, IL-10 and arginase I gene expression (P<0.05), indicating low levels of M2 macrophage. The results confirm the role of macrophages in the protective effects of dendrosomal curcumin against metastatic breast cancer in mice.
Keywords
Dendrosomal curcumin; macrophage; breast cancer; BALB/c mice;
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1 Bounaama A, Djerdjouri B, Laroche-Clary A, Le Morvan V, Robert J (2012). Short curcumin treatment modulates oxidative stress, arginase activity, aberrant crypt foci, and TGF-${\beta}$1 and HES-1 transcripts in 1, 2-dimethylhydrazine-colon carcinogenesis in mice. Toxicol, 302, 308-17.   DOI
2 Colombo MP, Trinchieri G (2002). Interleukin-12 in anti-tumor immunity and immunotherapy. Cytokine Growth Factor Rev, 13, 155-68.   DOI
3 Cui Y-L, Li H-K, Zhou H-Y, Zhang T, Li Q (2013). Correlations of tumor-associated macrophage subtypes with liver metastases of colorectal cancer. Asian Pac J Cancer Prev, 14, 1003-7.   DOI   ScienceOn
4 Ghalandarlaki N, Alizadeh AM, Ashkani-Esfahani S (2014). Nanotechnology-applied curcumin for different diseases therapy. Bio Med Res Int, 2014, 394264
5 Hao N-B, Lu M-H, Fan Y-H, et al (2012). Macrophages in tumor microenvironments and the progression of tumors. Clin Dev Immunol, 2012, 948098.
6 Heusinkveld M, van der Burg SH (2011). Identification and manipulation of tumor associated macrophages in human cancers. J Translat Med, 9, 216.   DOI
7 Huang Y, Lei Y, Zhang H, Zhang M, Dayton A (2011). Interleukin-12 treatment down-regulates STAT4 and induces apoptosis with increasing ROS production in human natural killer cells. J Leukocyte Biol, 90, 87-97.   DOI
8 Jagetia GC, Aggarwal BB (2007). "Spicing up" of the immune system by curcumin. J Clin Immunol, 27, 19-35.   DOI
9 Kamran MZ, Patil P, Gude RP (2013). Role of STAT3 in cancer metastasis and translational advances. Bio Med Res Int, 2013, 421821.
10 Kelloff GJ, Crowell JA, Steele VE, et al (2000). Progress in cancer chemoprevention: development of diet-derived chemopreventive agents. J Nutr, 130, 467-71.
11 Khaniki M, Azizian S, Alizadeh AM, et al (2013). The antiproliferative and anticancerogenic effects of nanocurcumin in rat colon cancer. Tehran Univers Med J, 71, 277-284.
12 Livak KJ, Schmittgen TD (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2-${\Delta}{\Delta}$CT method. Methods, 25, 402-8.   DOI
13 Martinez FO, Sica A, Mantovani A, Locati M (2007). Macrophage activation and polarization. Frontiers in Bioscience: J Virtual Library, 13, 453-61.
14 Medrek C, Ponten F, Jirstrom K, Leandersson K (2012). The presence of tumor associated macrophages in tumor stroma as a prognostic marker for breast cancer patients. BMC Cancer, 12, 306.   DOI
15 Mohsenikia M, Alizadeh AM, Khodayari S, et al (2013). The protective and therapeutic effects of alpha-solanine on mice breast cancer. Eur J Pharmacol, 718, 1-9.   DOI
16 Murray PJ, Wynn TA (2011). Protective and pathogenic functions of macrophage subsets. Nature Rev Immunol, 11, 723-37.   DOI   ScienceOn
17 Niu G, Wright KL, Ma Y, et al (2005). Role of Stat3 in regulating p53 expression and function. Mol Cell Bio, 25, 7432-40.   DOI   ScienceOn
18 Olefsky JM, Glass CK (2010). Macrophages, inflammation, and insulin resistance. Ann Rev Phys, 72, 219-46.   DOI
19 Sadeghizadeh M, Ranjbar B, Damaghi M, et al (2008). Dendrosomes as novel gene porters-III. J Chem Technol Biotechnol, 83, 912-20.   DOI
20 Sarbolouki MN, Sadeghizadeh M, Yaghoobi MM, et al (2000). Dendrosomes: a novel family of vehicles for transfection and therapy. J Chem Technol Biotechnol, 75, 919-22.   DOI
21 Schindler H, Lutz MB, Rollinghoff M, Bogdan C (2001). The production of IFN-${\gamma}$ by IL-12/IL-18-activated macrophages requires STAT4 signaling and is inhibited by IL-4. J Immunol, 166, 3075-82.   DOI
22 Sica A, Mantovani A (2012). Macrophage plasticity and polarization: in vivo veritas. J Clin Invest, 122, 787-95.   DOI   ScienceOn
23 Sica A, Schioppa T, Mantovani A, Allavena P (2006). Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy. Eur J Cancer, 42, 717-27.   DOI
24 Sinha P, Clements VK, Bunt SK, Albelda SM, Ostrand-Rosenberg S (2007). Cross-talk between myeloid-derived suppressor cells and macrophages subverts tumor immunity toward a type 2 response. J Immunol, 179, 977-83.   DOI
25 Siveen KS, Sikka S, Surana R, et al (2014). Targeting the STAT3 signaling pathway in cancer: Role of synthetic and natural inhibitors. Biochim Biophys Acta, 1845, 136-54.
26 Solinas G, Germano G, Mantovani A, Allavena P (2009). Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation. J Leukocyte Biol, 86, 1065-73.   DOI
27 Srivastava RM, Singh S, Dubey SK, Misra K, Khar A (2011). Immunomodulatory and therapeutic activity of curcumin. Intern Immunopharmacol, 11, 331-41.   DOI
28 Tu SP, Jin H, Shi JD, et al (2012). Curcumin induces the differentiation of myeloid-derived suppressor cells and inhibits their interaction with cancer cells and related tumor growth. Cancer Prev Res, 5, 205-15.   DOI   ScienceOn
29 Varalakshmi C, Ali AM, Pardhasaradhi B, et al (2008). Immunomodulatory effects of curcumin: In-vivo. Intern Immunopharmacol, 8, 688-700.   DOI   ScienceOn
30 Uddin S, Hussain AR, Manogaran PS, et al (2005). Curcumin suppresses growth and induces apoptosis in primary effusion lymphoma. Oncogene, 24, 7022-30.   DOI
31 Vasquez-Dunddel D, Pan F, Zeng Q, et al (2013). STAT3 regulates arginase-I in myeloid-derived suppressor cells from cancer patients. J Clin Invest, 123, 1580-9.   DOI
32 Vishvakarma NK, Singh SM (2010). Immunopotentiating effect of proton pump inhibitor pantoprazole in a lymphoma-bearing murine host: implication in antitumor activation of tumor-associated macrophages. Immunol Letters, 134, 83-92.   DOI
33 Wang W, Wang J, Dong S-f, et al (2010). Immunomodulatory activity of andrographolide on macrophage activation and specific antibody response. Acta Pharmacologica Sinica, 31, 191-201.   DOI
34 Weiss JM, Ridnour LA, Back T, et al (2010). Macrophage-dependent nitric oxide expression regulates tumor cell detachment and metastasis after IL-2/anti-CD40 immunotherapy. J Exp Med, 207, 2455-67.   DOI
35 Xu M, Mizoguchi I, Morishima N, et al (2010). Regulation of antitumor immune responses by the IL-12 family cytokines, IL-12, IL-23, and IL-27. J Immunol Res, 2010, 832454.
36 Yang C-L, Liu Y-Y, Ma Y-G, 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, 37960.   DOI
37 Yu H, Jove R (2004). The STATs of cancer-new molecular targets come of age. Nature Rev Cancer, 4, 97-105.   DOI
38 Zhang Y, Cheng S, Zhang M, et al (2013b). High-infiltration of tumor-associated macrophages predicts unfavorable clinical outcome for node-negative breast cancer. PloS One, 8, 76147.   DOI
39 Yu H, Pardoll D, Jove R (2009). STATs in cancer inflammation and immunity: a leading role for STAT3. Nature Rev Cancer, 9, 798-809.   DOI
40 Zhang X, Tian W, Cai X, et al (2013a). Hydrazinocurcumin encapsuled nanoparticles "re-educate" tumor-associated macrophages and exhibit anti-tumor effects on breast cancer following STAT3 suppression. PloS One, 8, 65896.   DOI
41 Alizadeh AM, Khaniki M, Azizian S, et al (2012). Chemoprevention of azoxymethane-initiated colon cancer in rat by using a novel polymeric nanocarrier-curcumin. European J Pharmacol, 689, 226-32.   DOI
42 Aggarwal BB, Sundaram C, Malani N, Ichikawa H (2007). Curcumin: the Indian solid gold. In The molecular targets and therapeutic uses of curcumin in health and disease (Springer), pp. 1-75.
43 Aggarwal BB, Sung B (2009). Pharmacological basis for the role of curcumin in chronic diseases: an age-old spice with modern targets. Trends Pharmacol Sci, 30, 85-94.   DOI
44 Alexandrow MG, Song LJ, Altiok S, et al (2012). Curcumin: a novel stat 3 pathway inhibitor for chemoprevention of lung cancer. Eur J Cancer Prev, 21, 407.   DOI
45 Alizadeh AM, Shiri S, Farsinejad S (2014). Metastasis review: from bench to bedside. Tumor Biol, 35, 8483-523.   DOI
46 Antony S, Kuttan R, Kuttan G (1999). Immunomodulatory activity of curcumin. Immunol Invest, 28, 291-303.   DOI
47 Babaei E, Sadeghizadeh M, Hassan ZM, et al (2012). Dendrosomal curcumin significantly suppresses cancer cell proliferation< i> in vitro and< i> in vivo. Int Immunopharmacol, 12, 226-34.   DOI
48 Bhattacharyya S, Hossain DMS, Mohanty S, et al (2010). Curcumin reverses T cell-mediated adaptive immune dysfunctions in tumor-bearing hosts. Cellular Mol Immunol, 7, 306-15.   DOI
49 Biswas SK, Chittezhath M, Shalova IN, Lim J-Y (2012). Macrophage polarization and plasticity in health and disease. Immunol Res, 53, 11-24.   DOI