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.
Highlights
Fulvic acid (FA) is a natural, acidic organic polymer extracted from humus found in soil, sediment, or aquatic environments [1,2]
The expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), which are regulated by the transcription factor NF-κB, in endothelial cells initiates the adhesion of cancer cells and monocytes to the endothelium [16,21,22]
We found that resistin activates NF-κB to induce ICAM-1 and VCAM-1 expression in HCT-116 cells, promoting colorectal cancer (CRC) cell adhesion to endothelial cells
Summary
Fulvic acid (FA) is a natural, acidic organic polymer extracted from humus found in soil, sediment, or aquatic environments [1,2]. The expression of ICAM-1 and VCAM-1, which are regulated by the transcription factor NF-κB, in endothelial cells initiates the adhesion of cancer cells and monocytes to the endothelium [16,21,22]. Our previous study showed that ICAM-1 and VCAM-1 were expressed in hepatocellular carcinoma (HCC) and promoted HCC cell adhesion to the endothelium [15]. ICAM-1 and VCAM-1 in both cancer and endothelial cells may play synergistic roles in metastasis progressions. We determined the effects of resistin and FA on the endothelium adhesion of human CRC cells and the underlying mechanism. We found that resistin activates NF-κB to induce ICAM-1 and VCAM-1 expression in HCT-116 cells, promoting CRC cell adhesion to endothelial cells. Our data reveal the resistin regulatory effects on CRC adhesion to the endothelium and suggest that FA may serve as a potential therapeutic candidate to inhibit the endothelium adhesion of CRC under resistin stimulation
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