ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
The aim of this study was to evaluate the effect of mouthrinse products containing deep sea water. We used original deep sea water (DSW) and processed deep sea water desalinated by reverse osmosis at one time (DDW-1), by reverse osmosis at two times (DDW-2) and concentrated by reverse osmosis (CDW). We made 2 kinds of mouthrinse products containing CDW and other agents for smell and taste and one product without deep sea water. The negative control was distilled water. In vivo study, the dental plaque index scores and the gingival index scores were reduced after 4 weeks mouthrinsing three times daily with 4 kinds of deep sea water and 3 kinds of mouthrinse products(p<0.05). The pH of dental plaque in 1 minute after mouthrinsing was not higher than 5.5 in all solutions, but the pH in 20 minutes after mouthrinsing was higher than 5.7 in DSW, CDW and 3 kinds of products which had higher mineral contents. In vitro study, the mouthrinse solutions containing the higher mineral contents were also the more effective in reduction of methyl mercaptan which is one of the causes of halitosis. The 2 kinds of products containing deep sea water killed Streptococcus mutans (ATCC 25175) in culture plates in one minute. These results indicate the usability of deep sea water in mouthrinses for oral hygiene management.