Pan-Pim Kinase Inhibitor AZD1208 Suppresses Tumor Growth and Synergistically Interacts with Akt Inhibition in Gastric Cancer Cells / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Pim kinases are highly conserved serine/threonine kinases, and different expression patterns of each isoform (Pim-1, Pim-2, and Pim-3) have been observed in various types of human cancers, including gastric cancer. AZD1208 is a potent and selective inhibitor that affects all three isoforms of Pim. We investigated the effects of AZD1208 as a single agent and in combination with an Akt inhibitor in gastric cancer cells. MATERIALS AND METHODS: The antitumor activity of AZD1208 with/without an Akt inhibitor was evaluated in a large panel of gastric cancer cell lines through growth inhibition assays. The underlying mechanism was also examined by western blotting, immunofluorescence assay, and cell cycle analysis. RESULTS: AZD1208 treatment decreased gastric cancer cell proliferation rates and induced autophagy only in long-term culture systems. Light chain 3B (LC3B), a marker of autophagy, was increased in sensitive cells in a dose-dependent manner with AZD1208 treatment, which suggested that the growth inhibition effect of AZD1208 was achieved through autophagy, not apoptosis. Moreover, we found that cells damaged by Pim inhibition were repaired by activation of the DNA damage repair pathway, which promoted cell survival and led the cells to become resistant to AZD1208. We also confirmed that the combination of an Akt inhibitor with AZD1208 produced a highly synergistic effect in gastric cancer cell lines. CONCLUSION: Treatment with AZD1208 alone induced considerable cell death through autophagy in gastric cancer cells. Moreover, the combination of AZD1208 with an Akt inhibitor showed synergistic antitumor effects through regulation of the DNA damage repair pathway.

Increased whole grain, fruits and vegetable intake reduced oxidative stress in high school students

There is increasing evidence that dietary factors in plant-based diets are important for the prevention of chronic disease. Especially, phytonutrients in fruits and vegetables have been recognized as major contributors for the decreased level of oxidative stress. In this study, the effect of switching the dietary habit to high consumption of fruits and vegetables were evaluated on the parameters of serum antioxidant status in healthy high school students. Forty one students participated in a randomized controlled trial and were assigned to the control group (n = 18) or the intervention group (n = 23). The intervention group was provided for 8 weeks with the main food source being whole grain and vegetables. Anthropometric measurements, blood parameters and dietary intakes were measured, and compared before and after study. After 8 weeks, weight and BMI were significantly decreased in the intervention group (p = 0.000). The serum diacron reactive oxygen metabolites (d-ROMs) test resulted in a significantly decreased level only in the intervention group (p < 0.05) after 8 weeks, but serum biological antioxidant potential (BAP) was increased significantly in both groups (p < 0.001). Intake of energy, total fat, cholesterol and sodium in the intervention group were significantly decreased after 8 weeks (p < 0.05). Also, the intervention group had significantly increased vitamin and phytonutrient intakes of all-trans-beta-carotene, alpha-carotene, alpha-tocopherol, ascorbic acid, and total phenols (p < 0.05). Overall, the results of this study suggest that whole grain, fruits, and vegetables supplementation showed improvement of the adolescent health.

Association between Hair Mineral Content and Nutritional Status in Vegetarians and Non-Vegetarians

Previous studies have shown that plant-based vegetarian diets, which typically contain a variety of antioxidants and dietary fiber, help reduce the risk of heart disease, diabetes, obesity, and cancer. However, some studies have reported that vegetarian diets can lead to deficiencies in protein and trace minerals compared to non-vegetarian diets. This study was conducted to compare anthropometric measurements, blood parameters, dietary intake, and hair mineral status in long-term vegetarians (MV; moderate vegan, LV; lacto-ovo vegetarian) and non-vegetarians (NV). Thirty MV (12 males, 18 females; mean age, 50.58 +/- 5.05 years), 15 LV (11 males, four females; mean age, 49.45 +/- 4.97 years), and 30 NV (15 males, 15 females; mean age, 48.90 +/- 3.62 years) participated. No significant differences were observed for age, height, weight, or body mass index, but body fat was significant lower in MV and LV males than that in NV males. White blood cell counts of MV, LV, and NV male subjects were significantly different. Dietary intake data showed that plant protein and plant iron intake were significantly higher in MV and LV than those in NV. Animal protein, animal fat, and animal iron intake were significantly higher in NV than those in MV and LV. A hair mineral analysis showed that calcium and iron were higher in the hair of MV and LV than those in NV. Zinc concentration in hair was not significantly different among the groups. The results suggest that vegetarian diets are adequate to sustain mineral status to at least the same degree as that of non-vegetarian diets.