Peroxisome proliferator-activated receptor (PPAR) ␦ is a member of the nuclear hormone receptor superfamily. PPAR␦ may ameliorate metabolic diseases such as obesity and diabetes. However, PPAR␦'s role in colorectal carcinogenesis remains controversial. Here, we present genetic and pharmacologic evidence demonstrating that deletion of PPAR␦ decreases intestinal adenoma growth in Apc Min/؉ mice and inhibits tumor-promoting effects of a PPAR␦ agonist GW501516. More importantly, we found that activation of PPAR␦ up-regulated VEGF in colon carcinoma cells. VEGF directly promotes colon tumor epithelial cell survival through activation of PI3K-Akt signaling. These results not only highlight concerns about the use of PPAR␦ agonists for treatment of metabolic disorders in patients who are at high risk for colorectal cancer, but also support the rationale for developing PPAR␦ antagonists for prevention and/or treatment of cancer.apoptosis ͉ colorectal cancer

Abstract. Curcumin has been found to exhibit anticancer activity and certain studies have shown that curcumin triggers the apoptosis of human A549 lung adenocarcinoma cells. However, the mechanism underlying curcumin-mediated apoptosis is not completely understood. The present study was designed to investigate the effect of curcumin on the induction of apoptosis and apoptosis-related factors in human A549 lung adenocarcinoma cells. Treatment of A549 cells with curcumin caused a concentration-dependent inhibition of cell growth and an increase in apoptosis, as confirmed by THE MTT assay, flow cytometry and morphology analysis. Curcumin-treatment of A549 cells induced a loss of the mitochondrial membrane potential and increased cytosolic cytochrome c. Furthermore, curcumin-induced apoptosis was accompanied by changes in intracellular oxidative stress-related enzymes, including decreased intracellular reactive oxygen species levels, increased superoxide dismutase and decreased malondialdehyde and 4-hydroxynonenal. In addition, induction of apoptosis was also accompanied by phosphorylation and activation of mitogen-activated protein kinase signaling pathway factors c-Jun N-terminal kinase, p38 and extracellular signal-regulated kinase. IntroductionLung cancer is the main leading cause of cancer-related fatality worldwide, with a rapidly increasing rate in China and other Asian countries (1-4). Chemotherapy is currently the most frequently used treatment for lung cancer and other types of cancer. However, while this method of treatment kills cancer cells, it also destroys some normal cells. Thus, the identification of novel natural compounds with low toxicity and high selectivity for killing cancer cells is a significant area in cancer research (5), and several natural products have been used as alternative treatments for cancer (6,7).Curcumin, a natural and crystalline compound isolated from the plant Curcuma longa, has been widely studied for its anti-inflammatory, antiangiogenic, antioxidant and anticancer effects in Chinese systems of medicine (8,9). Additionally, previous studies have shown that curcumin exhibits antiproliferative and anticarcinogenic properties in a wide variety of cell lines and animals (10,11). Previous studies have demonstrated that curcumin inhibits the growth and apoptosis of human A549 lung adenocarcinoma cells (12)(13)(14). However, the mechanisms of curcumin-induced apoptosis via oxidative stress remain unclear.The physiological status of the reactive oxygen species (ROS) levels can regulate cell proliferation: When intracellular ROS levels are above a certain threshold, ROS inhibit the cell cycle, leading to increased cell apoptosis and necrosis. In the tumor cells it often maintains a higher state of oxidation, with higher levels of oxygen free radicals and lower levels of the antioxidant enzyme activity. This higher oxidation state can activate certain transcription factors and associated genes, such as NF-κB and API, thus, ensuring the survival, proliferation and migration of tumor ...

No abstract

Antitumor activity of Capsaicin has been studied in various tumor types, but its potency in esophageal squamous cell carcinoma (ESCC) remains to be elucidated. Here, we explored the molecular mechanism of the capsaicin-induced antitumor effects on ESCC Eca109 cells. Eca109 cells were treated with capsaicin in vitro, the migration and invasion capacities were significantly decreased by scratch assay and transwell invasion assay. Meanwhile, matrix metalloproteinase (MMP)-9 (MMP-9) expression levels were also obviously down-regulated by Western blot. However, phosphorylated AMPK levels were significantly up-regulated, and this effect was eliminated by the AMPK inhibitor Compound C treatment. In addition, capsaicin can enhance sirtuin1 (SIRT1) expression, which could activate nuclear factor-κB (NF-κB) through deacetylation, and activate AMPK inducing the phosphorylation of IκBα and nuclear localization of NF-κB p65. Overall, these results revealed that Capsaicin can inhibit the migration and invasion of ESCC cells via the AMPK/NF-κB signaling pathway.

Background: The five-year survival rate of breast cancer is bleak because of the predilection for bone metastasis. Tumor-associated macrophages are involved in tumor metastasis and are divided into two antagonistic types, M1 and M2. This study aimed to detect the anti-tumor effect of the modified Sijunzi decoction (MSJZD) in a mouse model of breast cancer and explore whether MSJZD inhibited tumor metastasis by regulating macrophage polarization.Materials and methods: A luciferase-expressing mouse breast cancer cell line Luc-4T1 was inoculated into the right mammary fat pad of mice to establish a Balb/c mouse model of breast cancer. After inoculation for 24 h, the mice were randomly divided into the MSJZD group and control group (n = 5 per group). The mice in the MSJZD group were gavaged with 0.77 g/mL MSJZD once daily for 35 days, whereas those in the control group were administered the same volume of normal saline. Subsequently, the effects of MSJZD on tumor growth and macrophage polarization were investigated.Results: On day 35, MSJZD reduced tumor growth in the mouse model of breast cancer. Flow cytometry showed that the M1 marker (inducible nitric oxide synthase+) was increased in the MSJZD group relative to that in the control group, whereas the M2 marker (CD206+) did not exhibit significant differences between the two groups. The results indicated that MSJZD promoted macrophage polarization into the M1 phenotype.Conclusions: Our findings showed that MSJZD promoted macrophage polarization into the M1 phenotype, thus inhibiting tumor growth and metastasis in breast cancer.

Background: Natural astaxanthin (ASTA) has strong antioxidant properties and has been widely used as a health product to improve human health. However, the effects of ASTA on the reproductive performance of aging roosters have been poorly studied. We aimed to investigate the effects of dietary ASTA on semen quality and antioxidant capacity in aging roosters and to explore the potential mechanism of semen quality change via anti-oxidation defense system.Methods: In the present study, 96 53-week-old Jinghong No. 1 layer breeder roosters were fed a corn-soybean meal basal diet containing ASTA at 0, 25, 50, or 100 mg/kg for 6 week. Results: Semen quality in the ASTA groups remarkably improved as compared to those in the control group and antioxidant activities, the abilities to scavenge hydroxyl radicals and superoxide anions increased gradually with ASTA addition (P < 0.05). In addition, the mRNA levels of antioxidant enzymes, the mRNA and protein levels of the mitogen-activated protein kinase (MAPK), nuclear factor-erythroid 2-related factor 2 (Nrf2) were markedly increased in the 50-100 mg/kg ASTA group (P < 0.05). Conclusions: Collectively, these results demonstrate that dietary ASTA may improve semen quality by increasing antioxidant enzyme activities, and the ability to scavenge hydroxyl radicals, which may be related to up-regulation of the MAPK/Nrf2 pathway.