Pakistan Veterinary

Curcumin is widely known for its anticancer property but low aqueous solubility limits its use. In this study curcumin loaded solid lipid nanoparticles were used to overcome the defects of curcumin. The present study aimed at comparing the antitumor effect of nanocurcumin and curcumin. In vitro studies in DAL, A72 and HT29 cell lines confirmed the cytotoxic effect and in vivo studies were carried out in Dalton’s Ascites Lymphoma in mice. Antitumor effect was assessed by various parameters like cell block technique, AO/PI staining, TUNEL assay, immunocytochemistry, immunofluorescence and Real time PCR. AO/PI staining and TUNEL assay revealed increased number of apoptotic cells in curcumin and nanocurcumin group. Immunofluorescence staining revealed the nuclear migration of Nf-kB in tumor control whereas it showed cytoplasmic expression in treatment group. Immunocytochemistry revealed increase in expression of Bax and Caspase 8 whereas Bcl2, Cyclin D1 and PCNA showed lesser expression in nanocurcumin as compared to curcumin group. The expression pattern of miR181a, pre-miR-182, miR155 and some of the potential targets in the apoptotic pathway were analyzed by real time PCR. The qPCR analysis revealed the down regulation of miR 181a, 155, pre-miR182, Nf-kB and Bcl2 as well as up regulation of p53, Caspase 8 and caspase 9 in treatment group in which nanocurcumin group showed better effect as compared to curcumin group. The curcumin solid lipid nanoparticles delivered curcumin to cancer cells effectively and increased the therapeutic effect by applying its functions through miRNAs, induction of apoptosis as well as inhibition of metastasis. Thereby it is useful in providing target specific therapy and reduces the side effects of common methods.

[1]  H. Hemeg,et al.  Recent advancements of nanoparticles application in cancer and neurodegenerative disorders: At a glance. , 2022, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[2]  T. Ulutin,et al.  Anti-cancer effect of metformin on the metastasis and invasion of primary breast cancer cells through mediating NF-kB activity. , 2021, Acta histochemica.

[3]  A. Bahkali,et al.  PGMD/curcumin nanoparticles for the treatment of breast cancer , 2021, Scientific Reports.

[4]  A. Jemal,et al.  Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries , 2021, CA: a cancer journal for clinicians.

[5]  Chang Zhou,et al.  Curcumin promotes cell cycle arrest and apoptosis of acute myeloid leukemia cells by inactivating AKT , 2021, Oncology reports.

[6]  S. Müller,et al.  Epigenetic Mechanisms in Canine Cancer , 2020, Frontiers in Oncology.

[7]  I. Kaur,et al.  Enhancing Bioavailability and Stability of Curcumin Using Solid Lipid Nanoparticles (CLEN): A Covenant for Its Effectiveness , 2020, Frontiers in Bioengineering and Biotechnology.

[8]  M. Sadeghizadeh,et al.  Curcumin loaded PEG 400 ‐OA nanoparticles: A suitable system to increase apoptosis, decrease migration, and deregulate miR‐125b/miR182 in MDA‐MB‐231 human breast cancer cells , 2020 .

[9]  G. Wood,et al.  MicroRNA profiling in canine multicentric lymphoma , 2019, PloS one.

[10]  Y. Hu,et al.  MicroRNA-181 Functions as an Antioncogene and Mediates NF-κB Pathway by Targeting RTKN2 in Ovarian Cancers , 2018, Reproductive Sciences.

[11]  Yueyue Wang,et al.  Curcumin-Loaded Solid Lipid Nanoparticles Enhanced Anticancer Efficiency in Breast Cancer , 2018, Molecules.

[12]  G. Mattheolabakis,et al.  Curcumin formulated in solid lipid nanoparticles has enhanced efficacy in Hodgkin's lymphoma in mice. , 2018, Archives of biochemistry and biophysics.

[13]  M. Debnath,et al.  Induction of apoptosis, anti-proliferation, tumor-angiogenic suppression and down-regulation of Dalton's Ascitic Lymphoma (DAL) induced tumorigenesis by poly-l-lysine: A mechanistic study. , 2018, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[14]  M. J. Masarudin,et al.  Curcumin Analog DK1 Induces Apoptosis in Human Osteosarcoma Cells In Vitro through Mitochondria-Dependent Signaling Pathway , 2018, Molecules.

[15]  Deep Pooja,et al.  Optimization of solid lipid nanoparticles prepared by a single emulsification-solvent evaporation method , 2015, Data in brief.

[16]  W. Xue,et al.  MicroRNA181a Is Overexpressed in T-Cell Leukemia/Lymphoma and Related to Chemoresistance , 2015, BioMed research international.

[17]  Jianjun Chen,et al.  The pathological role and prognostic impact of miR-181 in acute myeloid leukemia. , 2015, Cancer genetics.

[18]  Christopher J. Cheng,et al.  Nanoparticle-based therapy in an in vivo microRNA-155 (miR-155)-dependent mouse model of lymphoma , 2012, Proceedings of the National Academy of Sciences.

[19]  Apeng Yang,et al.  Aberrant microRNA-182 expression is associated with glucocorticoid resistance in lymphoblastic malignancies , 2012, Leukemia & lymphoma.

[20]  L. Gordon,et al.  Curcumin nanodisk-induced apoptosis in mantle cell lymphoma , 2011, Leukemia & lymphoma.

[21]  C. Mohanty,et al.  The in vitro stability and in vivo pharmacokinetics of curcumin prepared as an aqueous nanoparticulate formulation. , 2010, Biomaterials.

[22]  D. Burstein,et al.  Evaluation of apoptosis in cytologic specimens , 2010, Diagnostic cytopathology.

[23]  S. Alahari,et al.  miRNA control of tumor cell invasion and metastasis , 2010, International journal of cancer.

[24]  B. Aggarwal,et al.  Curcumin (Diferuloylmethane) Down-Regulates Expression of Cell Proliferation and Antiapoptotic and Metastatic Gene Products through Suppression of IκBα Kinase and Akt Activation , 2006, Molecular Pharmacology.

[25]  Yan Chen,et al.  [Effect of curcumin on caspase 8- and caspase 9- induced apoptosis of lymphoma Raji cell]. , 2005, Zhongguo shi yan xue ye xue za zhi.

[26]  M. Belakavadi,et al.  Mechanism of inhibition of ascites tumor growth in mice by curcumin is mediated by NF-kB and caspase activated DNase , 2005, Molecular and Cellular Biochemistry.

[27]  J. Diehl.  Cycling to Cancer with Cyclin D1 , 2002, Cancer biology & therapy.

[28]  S. Orrenius,et al.  Assessment of Apoptosis and Necrosis by DNA Fragmentation and Morphological Criteria , 2001, Current protocols in cell biology.

[29]  A. Giordano,et al.  Prognostic role of cyclin D1 in lung cancer. Relationship to proliferating cell nuclear antigen. , 1999, American journal of respiratory cell and molecular biology.

[30]  A. Sahebkar,et al.  Curcumin as a MicroRNA Regulator in Cancer: A Review. , 2016, Reviews of physiology, biochemistry and pharmacology.

[31]  B. Yelikar,et al.  Diagnostic utility of the cell block method versus the conventional smear study in pleural fluid cytology , 2012, Journal of cytology.