Anticancer Activity of Indeno1,2-b-Pyridinol Derivative as a New DNA Minor Groove Binding Catalytic Inhibitor of Topoisomerase IIα

Topoisomerase IIα has been a representative anti-cancer target for decades thanks to its functional necessity in highly proliferative cancer cells. As type of topoisomerase IIα targeting drugs, topoisomerase II poisons are frequently in clinical usage. However, topoisomerase II poisons result in crucial consequences resulted from mechanistically induced DNA toxicity. For this reason, it is needed to develop catalytic inhibitors of topoisomerase IIα through the alternative mechanism of enzymatic regulation. As a catalytic inhibitor of topoisomerase IIα, AK-I-191 was previously reported for its enzyme inhibitory activity. In this study, we clarified the mechanism of AK-I-191 and conducted various types of spectroscopic and biological evaluations for deeper understanding of its mechanism of action. Conclusively, AK-I-191 represented potent topoisomerase IIα inhibitory activity through binding to minor groove of DNA double helix and showed synergistic effects with tamoxifen in antiproliferative activity.

Anticancer Activity of Indeno1,2-b-Pyridinol Derivative as a New DNA Minor Groove Binding Catalytic Inhibitor of Topoisomerase IIα

Topoisomerase IIα has been a representative anti-cancer target for decades thanks to its functional necessity in highly proliferative cancer cells. As type of topoisomerase IIα targeting drugs, topoisomerase II poisons are frequently in clinical usage. However, topoisomerase II poisons result in crucial consequences resulted from mechanistically induced DNA toxicity. For this reason, it is needed to develop catalytic inhibitors of topoisomerase IIα through the alternative mechanism of enzymatic regulation. As a catalytic inhibitor of topoisomerase IIα, AK-I-191 was previously reported for its enzyme inhibitory activity. In this study, we clarified the mechanism of AK-I-191 and conducted various types of spectroscopic and biological evaluations for deeper understanding of its mechanism of action. Conclusively, AK-I-191 represented potent topoisomerase IIα inhibitory activity through binding to minor groove of DNA double helix and showed synergistic effects with tamoxifen in antiproliferative activity.

Proposal of Dual Inhibitor Targeting ATPase Domains of Topoisomerase II and Heat Shock Protein 90

There is a conserved ATPase domain in topoisomerase II (topo II) and heat shock protein 90 (Hsp90) which belong to the GHKL (gyrase, Hsp90, histidine kinase, and MutL) family. The inhibitors that target each of topo II and Hsp90 are intensively studied as anti-cancer drugs since they play very important roles in cell proliferation and survival. Therefore the development of dual targeting anti-cancer drugs for topo II and Hsp90 is suggested to be a promising area. The topo II and Hsp90 inhibitors, known to bind to their ATP binding site, were searched. All the inhibitors investigated were docked to both topo II and Hsp90. Four candidate compounds as possible dual inhibitors were selected by analyzing the molecular docking study. The pharmacophore model of dual inhibitors for topo II and Hsp90 were generated and the design of novel dual inhibitor was proposed.

Association of curry consumption with blood lipids and glucose levels

BACKGROUND/OBJECTIVES: Curcumin, an active ingredient in turmeric, is highly consumed in South Asia. However, curry that contains turmeric as its main spice might be the major source of curcumin in most other countries. Although curcumin consumption is not as high in these countries as South Asia, the regular consumption of curcumin may provide a significant health-beneficial effect. This study evaluated whether the moderate consumption of curry can affect blood glucose and lipid levels that become dysregulated with age. SUBJECTS/METHODS: This study used data obtained from the Korea National Health and Nutrition Examination Survey, conducted from 2012 to 2013, to assess curry consumption frequency as well as blood glucose and blood lipid levels. The levels of blood glucose and lipids were subdivided by age, sex, and body mass index, and compared according to the curry consumption level. The estimates in each subgroup were further adjusted for potential confounding factors, including the diagnosis of diseases, physical activity, and smoking. RESULTS: After adjusting for the above confounding factors, the blood glucose and triglyceride levels were significantly lower in the moderate curry consumption group compared to the low curry consumption group, both in older (> 45) male and younger (30 to 44) female overweight individuals who have high blood glucose and triglyceride levels. CONCLUSIONS: These results suggest that curcumin consumption, in an ordinary diet, can have health-beneficial effects, including being helpful in maintaining blood glucose and triglyceride levels that become dysregulated with age. The results should be further confirmed in future studies.

Estimation of curcumin intake in Korea based on the Korea National Health and Nutrition Examination Survey (2008-2012)

BACKGROUND/OBJECTIVES: Turmeric and its active component curcumin have received considerable attention due to their many recognized biological activities. Turmeric has been commonly used in food preparation and herbal remedies in South Asia, leading to a high consumption rate of curcumin in this region. However, the amount of curcumin in the Korean diet has not yet been estimated, where turmeric is not a common ingredient. SUBJECTS/METHODS: This study utilized the combined data sets obtained from the Korea National Health and Nutrition Examination Survey conducted from 2008 to 2012 in order to estimate the curcumin intake in the Korean diet. The mean intake of curcumin was estimated from the amount of curcumin-containing foods (curry powder and ready-made curry) consumed using reported curcumin content in commercial turmeric and curry powders. RESULTS: Only 0.06% of Koreans responded that they consumed foods containing curcumin in a given day, and 40% of them were younger than 20 years of age. Curcumin-containing foods were largely prepared at home (72.9%) and a significant proportion (20.4%, nearly twice that of all other foods) was consumed as school and workplace meals. The estimated mean turmeric intake was about 0.47 g/day corresponding to 2.7-14.8 mg curcumin, while the average curry powder consumption was about 16.4 g, which gave rise to curcumin intake in the range of 8.2-95.0 mg among individuals who consumed curcumin. The difference in estimated curcumin intake by using the curcumin content in curry powder and turmeric may reflect that curry powder manufactured in Korea might contain higher amounts of other ingredients such as flour, and an estimation based on the curcumin content in the turmeric might be more acceptable. CONCLUSIONS: Thus, the amount of curcumin that can be obtained from the Korean diet in a day is 2.7-14.8 mg, corresponding to nearly one fourth of the daily curcumin intake in South Asia, although curcumin is rarely consumed in Korea.