Background: Green Curmin is a soluble curcumin extract product made in Thailand that has been reported to reduce gastric inflammation. Inflammatory cytokines including IL-1α , IL-6, and TNF-β play a crucial role in cancer cell migration, which is a major development towards poor prognosis. The aim of this study is to investigate the effects of Green Curmin on colon cancer cell growth and migration, which involve pro-inflammatory cytokines. Methods: Curcuma longa L. were extracted and named Green Curmin. The cytotoxicity of the Green Curmin-treated HCT116-colon cancer cells was obtained by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and flow cytometry. The effect of the extract on cancer migration was investigated with a wound-healing assay. In addition, fibroblastassociated cancer migration was confirmed by using the Transwell migration assay. Proinflammatory cytokines were also determined. Results: Green Curmin had cytotoxicity in the induced-cancer cell apoptosis at concentrations of 1 and 5 mg/ml. However, reduced colon cancer migration and fibroblast associated-cancer migration was found at concentrations of 0. 05 and 0. 1 mg/ml (non-toxicity dose), respectively. They also suppressed pro-inflammatory cytokines expression including IL-1α , IL-6, and TNF-β in colon cancer cells and IL-6 in fibroblast cells. Conclusion: Green Curmin has the potential to suppress pro-inflammatory cytokines and reduce fibroblast associated-cancer migration.

Introduction: Understanding the key role of the tumor microenvironment in specifying molecular markers of breast cancer subtypes is of a high importance in diagnosis and treatment. Therefore, the possibility of interconversion of luminal states and their specific markers alteration under the control of tumor microenvironment (TME), particularly cancer-associated fibroblasts (CAFs) deserves to be further investigated. Methods: To activate normal human fibroblasts, liquid overlay technique or nemosis was used and α-SMA protein expression, CAFs marker, in fibroblastic spheroids was measured by blotting. The luminal A, MCF-7, and luminal B, MDA-MB 361, cell lines were treated with normal and spheroidal/activated fibroblast conditioned medium for 48 hours. The morphological changes of both luminal A and B cells were evaluated by invert light microscopy and analyzed through the shape factor formula. Moreover, chemo-sensitivity, proliferation, and changes in ER-related and proliferative genes expression levels were assessed respectively via MTT assay, Ki67 expression Immunofluorescence assay, real time PCR and Annexin V-FITC techniques. Results: Activated (spheroidal) fibroblasts, expressed αSMA marker two folds more than monolayer cultured fibroblasts. Our study indicated a significant increase in IC50 of both luminal A and B cell lines after being treated with conditioned medium particularly in treated group with spheroidal conditioned medium. Studying Morphological changes using shape factor formula demonstrated more aggressiveness with gaining mesenchymal features in both luminal A and B subtypes by increasing exposure time. Changes in the expression of Ki67 were observed following treatment with fibroblastic and spheroidal paracrine secretome. Driven Data from Ki67 assay supports the luminal A and B interconversion by elevated Ki67 expression in luminal A and lowered Ki67 expression in luminal B. Gene expression analysis revealed that anti-apoptotic Bcl2 gene expression in both luminal types treated with condition medium has been increased though there has seen no interchange in expression of ER-related and proliferative genes between luminal A (MCF7) and luminal B (MDA-MB361) subtypes, the results of Annexin V-FITC flow cytometry test indicated a decrease in the population of both early and late apoptotic cells in groups treated with both fibroblastic and spheroidal condition medium compared to of control group. Conclusion: Under the paracrine influence of fibroblast cells, both luminal A (MCF7) and luminal B (MDA-MB) subtypes of breast cancer gained invasive, anti-apoptotic, and chemoresistance features which are mostly increased by activated(spheroidal) fibroblasts conditioned medium mimicking CAFs. There was no strong proof for interconversion of luminal A and luminal B which share more similarities among breast cancer molecular subtypes.