title: Curcumin exhibits anti-tumor effect and attenuates cellular migration via Slit-2 mediated down-regulation of SDF-1 and CXCR4 in endometrial adenocarcinoma cells.
abstract: 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.
authors.affiliation: Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow-226031, U.P., India.
authors.forename: Vijay Kumar
authors.initials: VK
authors.lastname: Sirohi
authors.affiliation: Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow-226031, U.P., India.
authors.forename: Pooja
authors.initials: P
authors.lastname: Popli
authors.affiliation: Department of Obstetrics & Gynaecology, King George's Medical University, Lucknow-226001, U.P., India.
authors.forename: Pushplata
authors.initials: P
authors.lastname: Sankhwar
authors.affiliation: Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow-226031, U.P., India.
authors.forename: Jyoti Bala
authors.initials: JB
authors.lastname: Kaushal
authors.affiliation: Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow-226031, U.P., India.
authors.forename: Kanchan
authors.initials: K
authors.lastname: Gupta
authors.affiliation: Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow-226031, U.P., India.
authors.forename: Murli
authors.initials: M
authors.lastname: Manohar
authors.affiliation: Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow-226031, U.P., India. Electronic address: anila.dwivedi@rediffmail.com.
authors.forename: Anila
authors.initials: A
authors.lastname: Dwivedi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D003474:Curcumin / Q000494:pharmacology*; D015536:Down-Regulation; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014709:Vero Cells; D023041:Xenograft Model Antitumor Assays; D000098552:Slit Homolog 2 Protein
chemical_list: C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D017382:Reactive Oxygen Species; D019718:Receptors, CXCR4; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D003474:Curcumin; D000098552:Slit Homolog 2 Protein
keywords: Cellular migration; Curcumin; Endometrial cancer; SDF-1; Slit-2