title: Fulvic Acid Attenuates Resistin-Induced Adhesion of HCT-116 Colorectal Cancer Cells to Endothelial Cells.
abstract: A high level of serum resistin has recently been found in patients with a number of cancers, including colorectal cancer (CRC). Hence, resistin may play a role in CRC development. Fulvic acid (FA), a class of humic substances, possesses pharmacological properties. However, the effect of FA on cancer pathophysiology remains unclear. The aim of this study was to investigate the effect of resistin on the endothelial adhesion of CRC and to determine whether FA elicits an antagonistic mechanism to neutralize this resistin effect. Human HCT-116 (p53-negative) and SW-48 (p53-positive) CRC cells and human umbilical vein endothelial cells (HUVECs) were used in the experiments. Treatment of both HCT-116 and SW-48 cells with resistin increases the adhesion of both cells to HUVECs. This result indicated that p53 may not regulate this resistin effect. A mechanistic study in HCT-116 cells further showed that this resistin effect occurs via the activation of NF-κB and the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Co-treating cells with both FA and resistin revealed that FA significantly attenuated the resistin-increased NF-κB activation and ICAM-1/VCAM-1 expression and the consequent adhesion of HCT-116 cells to HUVECs. These results demonstrate the role of resistin in promoting HCT-116 cell adhesion to HUVECs and indicate that FA might be a potential candidate for the inhibition of the endothelial adhesion of CRC in response to resistin.
authors.affiliation: Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan. wen1204@adm.cgmh.org.tw.|Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi 613, Taiwan. wen1204@adm.cgmh.org.tw.
authors.forename: Wen-Shih
authors.initials: WS
authors.lastname: Huang
authors.affiliation: Department of Neurosurgery, Chang Gung Memorial Hospital at Chiayi, Chang-Gung University College of Medicine, Chiayi 613, Taiwan. jents716@ms32.hinet.net.
authors.forename: Jen-Tsung
authors.initials: JT
authors.lastname: Yang
authors.affiliation: Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan. cclu999@gmail.com.|Division of Colorectal Surgery, Department of Surgery, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan. cclu999@gmail.com.
authors.forename: Chien-Chang
authors.initials: CC
authors.lastname: Lu
authors.affiliation: Department of Medical Research and Development, Chang Gung Memorial Hospital Chiayi Branch, Chiayi 613, Taiwan. sfchang@cgmh.org.tw.
authors.forename: Shun-Fu
authors.initials: SF
authors.lastname: Chang
authors.affiliation: Department of Biochemical Science and Technology, National Chiayi University, Chiayi 600, Taiwan. cnchen@mail.ncyu.edu.tw.
authors.forename: Cheng-Nan
authors.initials: CN
authors.lastname: Chen
authors.affiliation: Department of Orthopaedics and Traumatology, Taipei Veterans General Hospital &amp; School of Medicine, National Yang-Ming University, Taipei 112, Taiwan. ypsu@vghtpe.gov.tw.
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Su
authors.affiliation: Division of Colorectal Surgery, Department of Surgery, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan. kmch4329@gmail.com.
authors.forename: Ko-Chao
authors.initials: KC
authors.lastname: Lee
mesh_terms: D001578:Benzopyrans / Q000494:pharmacology*; D002448:Cell Adhesion; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D019743:Chemokines, CXC; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D052243:Resistin / Q000502:physiology*; D015533:Transcriptional Activation
chemical_list: D001578:Benzopyrans; C508524:CXCL17 protein, human; D018925:Chemokines; D019743:Chemokines, CXC; D016328:NF-kappa B; D052243:Resistin; D018799:Intercellular Adhesion Molecule-1; C005023:fulvic acid
keywords: colorectal carcinoma; fulvic acid; intercellular adhesion molecule-1; resistin; vascular cell adhesion molecule-1