DNA Topoisomerase Inhibitory Activity of Constituents from the Flowers of <i>Inula japonica</i>

Abstract

Key words Inula japonica; topoisomerase I; topoisomerase IIInula japonica THUNB. (Asteraceae) is a traditional herbal medicine and is widely distributed in Korea, Japan and China, and the flowers of this plant have been used to relieve phlegm, peptic disorder, inflammation and detumescence.1) Some terpenes 2-7) and flavonoids 8,9) have previously been isolated from this medicinal plant and have been reported to possess diverse biological activities, such as anti-diabetes, 10) antihypolipidemia, 11) hepatoprotective, 12) anti-inflammatory 7) and anti-tumor 1,2,13) effects. We have been isolating compounds that inhibited topoisomerases I and II from the source of medicinal plants. [14][15][16][17][18] DNA topoisomerases are enzymes that control DNA topology in the cell and are targets of anticancer drugs. 19,20) Topoisomerase I cleaves and reseals one DNA strand at a time and does not require ATP for the complementary strand to pass through the enzyme-linked strand break, thereby effecting DNA relaxation. Topoisomerase II cleaves both strands of DNA during catalysis. In a reaction coupled to ATP binding and hydrolysis, these proteins cleave one DNA duplex, transport a second duplex through the break, and then religate the cleaved duplex. 21) Camptothecin (CPT) and etoposide (VP-16) are typical inhibitors of topoisomerases I and II, respectively. 19) In this paper, we report isolation of fourteen compounds from the flowers of I. japonica and their DNA topoisomerases I and II inhibitory activities and cytotoxicities. Results and DiscussionTwo new (1, 2) and twelve known compounds (3-14) were isolated by various chromatographic separations from the EtOAc extract of the flowers of I. japonica (Fig. 1) C-NMR and distortionless enhancement by polarization transfer (DEPT) spectra of 1 showed seventeen peaks due to three methyl, four methylene, five methine and five quaternary carbons. The corresponding proton signals were determined by 1 H-detected heteronuclear multiple quantum coherence (HMQC) spectrum.The

Antiproliferative activities of Amaryllidaceae alkaloids from Lycoris radiata targeting DNA topoisomerase I

“…3, hippeastrine and camptothecin exhibited inhibitory activity on Top I in a similar dose-dependent manner with the IC 50 values at 7.25 ± 0.20 μg/mL and 6.72 ± 0.23 μg/mL, respectively, which clearly implied that hippeastrine was found to be comparable with the well known anticancer drug camptothecin in terms of IC 50 . Other tests on camptothecin against Top I also showed similar inhibitory activity levels with the IC 50 values at 8.71 μg/mL35 or 8.53 μg/mL36, which could further approve our finding in this work. Hence, our result confirmed that hippeastrine could be a potential Top I inhibitor as a very promising anticancer drug candidate, which is in good consistent with the enrichment factors based on UF-LC/MS assay and provides a good validation for its effectiveness.…”

In vitro cell viability by CellProfiler®software as equivalent to MTT assay

“…[ 28 ] showed an IC 50 of 0.56 μM for camptothecin in a human liver cancer line and Piao et al . [ 31 ] found an IC 50 of 0.70 μM for the same lineage. In addition, Fronza et al .…”

Induction of cell cycle arrest and apoptosis by tomentosin in hepatocellular carcinoma HepG2 and Huh7 cells

“…Tomentosin is a phytochemical sesquiterpene lactone mainly found in medicinal herbs, such as Arnica longifolia , Inula japonica , Inula viscosa , and Xanthium strumarium . 26 –29 Tomentosin is known to exert anticancer activity in several types of cancer cells. 16 According to a recent report, tomentosin induces apoptosis and increases the SubG0 and G2/M population in human melanoma cell lines.…”