Curcumin exhibits anti-tumor effect and attenuates cellular migration via Slit-2 mediated down-regulation of SDF-1 and CXCR4 in endometrial adenocarcinoma cells

• Published in: The Journal of nutritional biochemistry 2017-06, Vol.44, p.60-70
• Main Authors: Sirohi, Vijay Kumar, Popli, Pooja, Sankhwar, Pushplata, Kaushal, Jyoti Bala, Gupta, Kanchan, Manohar, Murli, Dwivedi, Anila
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; Cell Line, Tumor; Cell Movement - drug effects; Cell Survival - drug effects; Cellular migration; Cercopithecus aethiops; Chemokine CXCL12 - genetics; Chemokine CXCL12 - metabolism; Curcumin; Curcumin - pharmacology; Down-Regulation; Endometrial cancer; Endometrial Neoplasms - drug therapy; Endometrial Neoplasms - genetics; Female; Gene Expression Regulation, Neoplastic; Humans; Intercellular Signaling Peptides and Proteins - genetics; Intercellular Signaling Peptides and Proteins - metabolism; Matrix Metalloproteinase 2 - genetics; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; Mice; Mice, Inbred NOD; Mice, SCID; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Reactive Oxygen Species - metabolism; Receptors, CXCR4 - genetics; Receptors, CXCR4 - metabolism; SDF-1; Signal Transduction; Slit-2; Vero Cells; Xenograft Model Antitumor Assays
• ISSN: 0955-2863; 1873-4847
• DOI: 10.1016/j.jnutbio.2016.12.021

Although curcumin shows anti-proliferative and anti-inflammatory activities in various cancers, the effect of curcumin on cellular migration in endometrial adenocarcinoma cells remains to be understood. The current investigation was aimed to explore the anti-proliferative and anti-migratory effects of curcumin and its mechanism of action in endometrial cancer cells. Our in-vitro and in-vivo experimental studies showed that curcumin inhibited the proliferation of endometrial cancer cells and suppressed the tumor growth in Ishikawa xenograft mouse model. Curcumin induced ROS-mediated apoptosis in endometrial cancer cells. Curcumin suppressed the migration rate of Ishikawa and Hec-1B cells as analyzed by scratch wound assay. In transwell migration studies, knock down of Slit-2 reversed the anti-migratory effect of curcumin in these cell lines. Curcumin significantly up-regulated the expression of Slit-2 in Ishikawa, Hec-1B and primary endometrial cancer cells while it down-regulated the expression of stromal cell-derived factor-1 (SDF-1) and CXCR4 which in turn, suppressed the expression of matrix metallopeptidases (MMP) 2 and 9, thus attenuating the migration of endometrial cancer cells. In summary, we have demonstrated that curcumin has inhibitory effect on cellular migration via Slit-2 mediated down-regulation of CXCR4, SDF-1, and MMP2/MMP9 in endometrial carcinoma cells. These findings helped explore the role of Slit-2 in endometrial cancer cells.