Li Liu

Purpose Obesity, substantially increasing the risk of diseases such as metabolic diseases, becomes a major health challenge. In this study, we, therefore, investigated the effect of modified apple polysaccharide (MAP) on obesity. Methods Twelve male C57BL/6J mice were given a 45% high-fat diet (HFD) for 12 weeks to replicate an obesity model and six mice were given normal diet as control. Then, 1 g/kg MAP was administrated to six mice by gavage for 15 days. Illumina Miseq PE300 sequencing platform was used to analyze the microbial diversity of fecal samples. Flow cytometry was employed to investigate the effects of MAP on immune cells in adipose tissue. Bacterial culture and qPCR were used to assess the effects of MAP on the growth of whole fecal bacteria and representative microbiota in vitro. Results MAP could alleviate HFD-induced obesity and decrease body weight of mice effectively. The results of α diversity showed that Shannon index in HFD group was significantly lower than that in control group; Shannon index in MAP group was higher than that in HFD group. The results of β diversity showed that the microbiota of MAP group was more similar to that of control group. HFD increased the number of T cells and macrophages in adipocytes; while MAP decreased the number of T cells and macrophages. MAP could promote the growth of fecal bacteria, and demonstrated a facilitated effect on the proliferation of Bacteroidetes, Bacteroides, Lactobacillus, and an inhibitory effect on Fusobacterium. Conclusions MAP could reduce HFD-induced obesity of mice effectively. The possible mechanisms are that MAP restored HFD-induced intestinal microbiota disorder, downregulated the number of T cells and macrophages in adipose tissue.

Abstract:  Multiple studies have pointed out that dietary components could inhibit cancer progression and metastasis, and it has been proven that many ingredients of apple have benefits for cancer prevention. We, therefore, extracted modified apple polysaccharides (MAP) from apple and hypothesized that MAP have a cancer‐preventive effect as do other ingredients of apple. Three human colorectal cancer cell lines: SW‐1116, HT‐29, and Caco‐2 were exposed to different concentrations of MAP (0% to 0.1%). Inhibition of cell proliferation was measured by 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay. DNA fragmentation was visualized by agarose‐gel electrophoresis. The amount of apoptotic cells was assessed by flow cytometry, and protein level of caspase 3, 8, 9, Bax, and Bcl‐2 was evaluated by Western blot. At the concentrations of 0.01% to 0.1%, MAP showed growth‐inhibiting and apoptosis‐inducing effects on cancer cells. It increased the expression of caspase 3, 8, 9, and Bax, while decreased of Bcl‐2, which denoted that MAP may induce apoptosis through both the mitochondrial‐mediated and death receptor‐mediated apoptotic ways. These data indicate that MAP has the potential for clinical prevention and treatment for colon cancer.

This study aimed to observe the growth‐inhibitory effect of PC‐407 (4‐[5‐naphthyl‐3‐(trifluoromethyl)‐1H‐pyrazol‐1‐yl] benzenesulfonamide), a celecoxib derivative synthesized in our lab, in human colorectal cancer cells and a colitis‐associated colorectal cancer (CACC) model, and investigate the relative molecular mechanisms. SW‐1116 (expressing a high level of cyclooxygenase‐2 [COX‐2]), HT‐29 (expressing a moderate level of COX‐2), and SW‐480 (no expression of COX‐2) cell lines were exposed to different concentrations of celecoxib (0–100 μmol/L) or PC‐407 (0–100 μmol/L). Then, COX‐2 levels were assessed by reverse transcription‐PCR and Western blotting. COX‐2 activity was evaluated by measuring prostaglandin E₂ concentration using enzyme‐linked immunoassay. A mouse model of colitis‐associated carcinogenesis was employed to determine the effect of PC‐407 in vivo. PC‐407 inhibited cell growth in a concentration‐dependent manner, and the IC₅₀ values of PC‐407 for growth inhibition of SW‐1116, HT‐29, and SW‐480 cells were 17.60 ± 3.02, 18.14 ± 2.81, and 8.13 ± 0.40 μmol/L, respectively. PC‐407 down‐regulated COX‐2 mRNA and protein levels and reduced prostaglandin E₂ production significantly. In vivo, PC‐407 inhibited the genesis of CACC effectively. Our data indicate that PC‐407 can inhibit the growth of tumor both in vitro and in vivo and suggest that the effect probably involves inhibition of the COX‐2 pathway and other COX‐2‐independent pathways. (Cancer Sci 2009; 100: 2451–2458)