Premium
Phytosomal‐curcumin antagonizes cell growth and migration, induced by thrombin through AMP‐Kinase in breast cancer
Author(s) -
Hashemzehi Milad,
BehnamRassouli Reihane,
Hassanian Seyed Mahdi,
MoradiBinabaj Maryam,
MoradiMarjaneh Reyhaneh,
Rahmani Farzad,
Fiuji Hamid,
Jamili Mahdi,
Mirahmadi Mahdi,
Boromand Nadia,
Piran Mehran,
Jafari Mohieddin,
Sahebkar Amirhossein,
Avan Amir,
Khazaei Majid
Publication year - 2018
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.26796
Subject(s) - curcumin , chemistry , ampk , cell growth , cancer research , pharmacology , protein kinase a , kinase , microbiology and biotechnology , biology , biochemistry
Abstract Here we explored the antitumor‐activity of novel‐formulated‐form of curcumin (phytosomal‐encapsulated‐curcumin) or in combination with 5‐FU in breast cancer. The antiproliferative activity was assessed in 2D and 3‐dimensional cell‐culture‐model. The migratory‐behaviors of the cells were determined by migration assay. The expression levels of CyclinD1,GSK3a/b, P‐AMPK, MMP9, and E‐cadherin were studied by qRT‐PCR and/or Western blotting. The anti‐inflammatory of nano‐curcumin was assessed, while antioxidant activity was evaluated by malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and total thiols (T‐SH). To understand dynamic behavior of genes, we reconstructed a Boolean network, while the robustness of this model was evaluated by Hamming distance. phytosomal‐curcumin suppressed cell‐growth followed by tumor‐shrinkage in 3D model through perturbation of AMP‐activated protein kinase. Curcumin reduced the invasiveness of MCF‐7 through perturbation of E‐cadherin. Moreover, phytosomal‐curcumin inhibited the tumor growth in xerograph model. Histological staining of tumor tissues revealed vascular disruption and RBC extravasation, necrosis, tumor stroma, and inflammation. Co‐treatment of curcumin and 5‐FU reduced the lipid‐peroxidation and increased MDA/SOD level. Of note, curcumin reduced cyclinD‐expression in breast cancer cell treated with thrombin, and activates AMPK in a time‐dependent manner. Also suppression of AMPK abrogated inhibitory effect of phytosomal‐curcumin on thrombin‐induced cyclin D1 over‐expression, suggesting that AMPK is essential for anti‐proliferative effect of this agent in breast cancer. Our finding demonstrated that phytosomal‐curcumin antagonizes cell growth and migration, induced by thrombin through AMP‐Kinase in breast cancer, supporting further‐investigations on the therapeutic potential of this novel anticancer agent in treatment of breast cancer.