Breaking the balance between proliferation and differentiation in animal cells can lead to cancer, but the mechanisms maintaining this balance remain largely undefined. The calcium activated chloride channel A1 (CLCA1) is a member of the calcium sensitive chloride conductance family of proteins and is expressed mainly in the colon, small intestine and appendix. We show that CLCA1 plays a functional role in differentiation and proliferation of Caco-2 cells and of intestinal tissue. Caco-2 cells spontaneously differentiate either in confluent culture or when treated with butyrate, a molecule present naturally in the diet. Here, we compared CLCA1 expressional levels between patients with and without colorectal cancer (CRC) and determined the functional role of CLCA1 in differentiation and proliferation of Caco-2 cells. We showed that: 1) CLCA1 and CLCA4 expression were down-regulated significantly in CRC patients; 2) CLCA1 expression was up-regulated in Caco-2 cells induced to differentiate by confluent culture or by treatment with sodium butyrate (NaBT); 3) Knockdown of CLCA1 with siRNA significantly inhibited cell differentiation and promoted cell proliferation in Caco-2 confluent cultures, and 4) In Caco-2 3D culture, suppression of CLCA1 significantly increased cell proliferation and compromised NaBT-induced inhibition of proliferation. In conclusion, CLCA1 may contribute to promoting spontaneous differentiation and reducing proliferation of Caco-2 cells and may be a target of NaBT-induced inhibition of proliferation and therefore a potential diagnostic marker for CRC prognosis.

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The transition from proliferation to differentiation in colorectal cancer is regulated by the calcium activated chloride channel A1

Although Morus bombycis koidzumi (MB) extract has been reported to have antioxidant activity, the mechanism underlying its antioxidant activity has not been elucidated. In this report, we showed that FOXO3a was activated by MB extract. FOXO3a is a transcription factor that is involved in various biological functions such as cell cycle control, apoptosis, DNA repair, and reactive oxygen species (ROS) detoxification. Protein levels of FOXO3a and MnSOD, target gene of FOXO3a were increased by the MB extract. The ROS level was decreased by the MB extract in human embryonic fibroblast (HEF) cells. Among components of the MB extract, oxyresveratrol (2′,4′,3,5-tetrahydroxystilbene) was identified and turned out to activate FOXO3a. The protein level of FOXO3a was increased by oxyresveratrol. Promoter activities of target genes of FOXO3a such as MnSOD, p27, and GADD45 were activated by oxyresveratrol. The ROS level was decreased by oxyresveratrol in HEF cells in a dose-dependent manner. However, the ROS le...

https://www.tandfonline.com/doi/pdf/10.1080/19768354.2016.1143030

FOXO3a Activation by oxyresveratrol of Morus bombycis koidzumi extract mediates antioxidant activity

In our previous report, Solidago virgaurea var. gigantea (SV) extract was shown to exhibit anti-adipogenesis activity in 3T3-L1 adipocyte cells. In this study, anti-obesity activity of SV extract was investigated in in vivo animal model. Sprague-Dawley (SD) rats were administered with high-fat diet, and the effect of SV extract was tested. SD rats were treated orally with SV extract for eight weeks, and their body weight was measured every week. The oral treatment of SV extract decreased body weight, fat tissue weight, blood low-density lipoprotein-cholesterol level, and blood triglycerides level. The p-AMP-activated protein kinase (AMPK) (AMP kinase) protein level in the fat tissue of the SV extract-treated SD rats increased. The protein levels of AMPK-downstream proteins, c-AMP response element binding protein and acetyl-CoA carboxylase, fatty acid synthase, and FABP4 decreased, indicating that SV extract-activated AMPK induced inhibition of adipogenesis and lipid biosynthesis in fat tissue. 1H-...

Anti-obesity effect of Solidago virgaaurea extract in high-fat diet-fed SD rat

PC12 cells were differentiated into the cells of chromaffin phenotype by butyrate treatment. Cells were aggregated and formed tight cell adhesion. To investigate the molecular change in this differentiation, we examined expression levels of cell adhesion proteins and extracellular proteins during butyrate induced-differentiation of PC12 cells. Integrin β1, integrin α7, E cadherin, VCAM, collagen-I, fibronectin, desmoglein and connexin were increased during differentiation. The levels of clusterin and secreted clusterin were also increased. These increased levels of cell adhesion proteins and extracellular proteins appear to induce cell aggregation and tight cell adhesion. The levels of p21, p27 and p16 were increased probably because of differentiation-related growth arrest during differentiation. Prolonged incubation of butyrate up to 1 day was required for differentiation. Signal transduction pathways for this differentiatiom could not be identified since various inhibitors had no effect. The r...

Butyrate-induced differentiation of PC12 cells to chromaffin cells involves cell adhesion and induction of extracellular proteins and cell adhesion proteins

Hong Joon Kang

Papers

Butyrate-induced differentiation of PC12 cells to chromaffin cells involves cell adhesion and induction of extracellular proteins and cell adhesion proteins