Cover Image

Curcumin and Curcumin-Loaded Nanogel Induce Apoptosis Activity in K562 Chronic Myelogenous Leukemia Cells

Sepideh Khatamsaz, Mehrdad Hashemi

Background: Chronic myeloid leukemia (CML), a hematological cancer of stem cells, is caused by the activation of oncogenic factors alone or/with inactivation of tumor suppressor genes. Curcumin is a hydrophobic polyphenol and the main compound of turmeric, which has been used in daily diets for many years. It is also a safe drug. Nanogels and nanobiotechnology have important roles in the diagnosis and treatment of diseases and drug delivery. Materials and Methods: To prepare the nanodrug, chitosan nanogels were prepared in 1% acetic acid and cross-linked with stearate by 1- ethyl- 3 (3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). Subsequently, curcumin was loaded in the chitosan-stearate nanogel. Physical and morphological characteristics of the nanodrug were determined by transmission electron microscopy (TEM), dynamic light scattering (DLS), and Fourier transform infrared spectroscopy. Different nanodrug concentrations were prepared and evaluated on the K562 CML cell line. The apoptotic activities of curcumin and nanodrug on the cells were detected by flow cytometry, MTT assay, and trypan blue staining. Results: DLS revealed that the size of the nanodrug was 150 nm, which was confirmed by TEM. The half maximal inhibitory concentration (IC50) values of curcumin and nanodrug were 50 and 25 μg/ml, respectively P < 0.05). Apoptosis of the K562 cell line occurred at 48 h post-treatment with 25 μg/ml curcumin and 12.5 μg/ml nanodrug. Conclusion: The increase in the cytotoxicity of curcumin and nanodrug was directly related to the drug concentration and time. The nanodrug exhibited more cytotoxic effects on the vital capacity of the cells and stimulated more apoptosis compared with curcumin alone. [GMJ.2018;7:e921]

Curcumin; Chronic Myelogenous Leukemia; Nanogel; Chitosan; Stearate

- Talpaz M, Hehlmann R, Quintas-Cardama A, Mercer J, Cortes J. Re-emergence of interferon-α in the treatment of chronic myeloid leukemia. Leukemia. 2013; 27(4): 803-12.

- M Yallapu M, Jaggi M, C Chauhan S. Curcumin nanomedicine: a road to cancer therapeutics. Curr Pharm Des. 2013; 19(11): 1994-2010.

- 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.

- Teow SY, Liew K, Ali SA, Khoo AS, Peh SC. Antibacterial action of curcumin against Staphylococcus aureus: a brief review. J Trop Med. 2016; 2016: 2853045.

- Weber WM, Hunsaker LA, Abcouwer SF, Deck LM, Vander Jagt DL. Anti-oxidant activities of curcumin and related enones. Bioorg Med Chem. 2005; 13(11): 3811-20.

- Park W, Amin AR, Chen ZG, Shin DM. New perspectives of curcumin in cancer prevention. Cancer Prev Res. 2013; 6(5): 387-400.

- Ghosh AK, Kay NE, Secreto CR, Shanafelt TD. Curcumin inhibits pro-survival pathways in CLL B-cells and has the potential to overcome stromal protection of CLL B-cells in combination with EGCG. Clin Cancer Res. 2009; 15(4): 1250.

- Kakarala M, Brenner DE, Korkaya H, Cheng C, Tazi K, Ginestier C, et al. Targeting breast stem cells with the cancer preventive compounds curcumin and piperine. Breast cancer research and treatment. Breast Cancer Res Treat. 2010; 122(3): 777-85.

- Klonisch T, Wiechec E, Hombach-Klonisch S, Ande SR, Wesselborg S, Schulze-Osthoff K, et al. Cancer stem cell markers in common cancers–therapeutic implications. Trends Mol Med. 2008; 14(10): 450-60.

- Yallapu MM, Gupta BK, Jaggi M, Chauhan SC. Fabrication of curcumin encapsulated PLGA nanoparticles for improved therapeutic effects in metastatic cancer cells. J Colloid Interface Sci. 2010; 351(1): 19-29.

- Atabi F, Mousavi Gargari SL, Hashemi M, Yaghmaei P. Doxorubicin loaded DNA aptamer linked myristilated chitosan nanogel for targeted drug delivery to prostate cancer. Iran J Pharm Res. 2017; 18(2): 45-62.

- Banerjee B, Chakraborty S, Ghosh D, Raha S, Sen PC, Jana K. Benzo (a) pyrene induced p53 mediated male germ cell apoptosis: Synergistic protective effects of curcumin and resveratrol. Front Pharmacol. 2016; 7: 245.

- Entezari M, Khatamsaz S, Dehghani H. Anti-proliferative effects curcumin in human acute lymphoblastic leukemia cell line. Iran J Pharm Res. 2017; 8(2): 1-5.

- Hughes A, Yong AS. Immune effector recovery in chronic myeloid leukemia and treatment-free remission. Front Immunol. 2017; 8: 469.

- Guerra B, Martín-Rodríguez P, Díaz-Chico JC, McNaughton-Smith G, Jiménez-Alonso S, Hueso-Falcón I, et al. CM363, a novel naphthoquinone derivative which acts as multikinase modulator and overcomes imatinib resistance in chronic myelogenous leukemia. Oncotarget. 2017; 8(18): 29679.

- 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.

- Bakhshayesh M, Zaker F, Hashemi M, Katebi M, Solaimani M. TGF-β1–mediated Apoptosis Associated With SMAD-dependent MitochondrialBcl-2 Expression. Clin Lymphoma Myeloma Leuk. 2012; 12(2): 138-43.

- Shishodia S, Chaturvedi MM, Aggarwal BB. Role of curcumin in cancer therapy. Curr Probl Cancer. 2007; 31(4): 243-305.

- Yallapu MM, Jaggi M, Chauhan SC. Curcumin nanoformulations: a future nanomedicine for cancer. Drug Discov Today. 2012; 17(1): 71-80.

-Entezari M, Atabi F. Preparation and characterization of myristoylated chitosan nanogel as carrier of silibinin for breast cancer therapy. Galen Medical Journal. 2017; 6(2): 136-44.

- Karmakar S, Banik NL, Ray SK. Curcumin suppressed anti-apoptotic signals and activated cysteine proteases for apoptosis in human malignant glioblastoma U87MG cells. Neurochem Res. 2007; 32(12): 2103-13.

- Bisht S, Khan MA, Bekhit M, Bai H, Cornish T, Mizuma M, et al. A polymeric nanoparticle formulation of curcumin (NanoCurc™) ameliorates CCl4-induced hepatic injury and fibrosis through reduction of pro-inflammatory cytokines and stellate cell activation. Lab Invest. 2011; 91(9): 1383-95.

- Karewicz A, Bielska D, Loboda A, Gzyl-Malcher B, Bednar J, Jozkowicz A, et al. Curcumin-containing liposomes stabilized by thin layers of chitosan derivatives. Colloids Surf B Biointerfaces. 2013; 109: 307-16.

- Zheng S, Gao X, Liu X, Yu T, Zheng T, Wang Y, et al. Biodegradable micelles enhance the antiglioma activity of curcumin in vitro and in vivo. Int J Nanomedicine. 2016; 11: 2721-36.

Refbacks

  • There are currently no refbacks.