Inhibitory effects of docosyl p-coumarate on DNA topoisomerase activity and human cancer cell growth

Abstract

Abstract. We previously found six compounds of alkyl pcoumarates from a composite plant Artemisia annua L., and chemically synthesized these compounds (cis-isomer of C20, C22 and C24, and trans-isomer of C20, C22 and C24 of pcoumarates are compounds 1-6, respectively). This report describes the inhibitory activities of these alkyl p-coumarates against DNA polymerase (pol), DNA topoisomerase (topo), and human cancer cell growth. Among the compounds tested, compounds 1 and 4 weakly inhibited repair-related pol ß activity, but no compound influenced the activity of replicative pol ·. Compounds 4-6 and compounds 2 and 5 were potent inhibitors of human topos I and II, respectively. Compounds 2, 4, 5 and 6 also suppressed the growth of human colon carcinoma cell line, HCT116, with or without p53, suggesting that cell growth inhibition had the same tendency as the inhibition of topos rather than pols. Compound 5 (docosyl p-coumarate), which was the strongest inhibitor of topo II and cancer cell growth in the compounds tested, halted HCT116 p53 +/+ cells in G2/M phases, and induced apoptosis, although this compound did not affect the cell cycle of HCT116 p53-/-cells. These results suggest that the effect of p53-dependent cell cycle arrest may be effective for topo inhibition by compound 5. From these findings, the action mode of alkyl pcoumarates as an anti-cancer agent is discussed.

Natural Products, Synthetic and Non-Nucleoside Compounds as Inhibitors of Enzymes Related to DNA: Update 2013

“…Compounds 95, 97 and 93 and 96 were potent inhibitors of human topos I and II, respectively. They also suppressed HCT116 human colon carcinoma cell line growth, with or without p53 inhibition, suggesting that cell growth inhibition had the same tendency as the topos inhibition [59].…”

Evaluation of leaf extracts of Artemisia afra Jacq. ex Willd. and Leucosidea sericea Eckl. Zeyh. for genotoxicity and the modulation of EMS-induced genotoxicity

“…However, in an in vitro experiment, ethanol extract of A. afra was cytotoxic against U937 and HeLa cancer cells via the decrease in mitochondrial membrane potential after G2/M arrest (Spies et al, 2013;Venables et al, 2016). Some Artemisia species and their active components that have been shown to arrest cells in in vitro experiments with cell lines include, A. sphaerocephala (Wang et al, 2017), A. princeps, cell cycle arrest at G2/M (Lee et al, 2013), A. monosperma, cell cycle arrest at S+G2/Mphase (Whelan and Ryan, 2004) and A. annua (Mizushina et al, 2010).…”

PTP1B Inhibitory Effect of Alkyl p-Coumarates from Calystegia soldanella

“…The PTPB inhibitory effect of samples was analyzed using the modified method of Burke et al [9]. A sample (3 μL in DMSO) was added to a reaction mixture containing 2 μL of 0.5 μg/mL enzyme, 10 μL of buffer (50 mM citrate, pH 6.0, 0.1 M NaCl, 1 mM EDTA, and 1 mM dithiothreitol), 35 μL of water, and 50 μL of 20 mM phosphatase substrate.…”

“…2, 20.2, 24.0, 29.4, and 36.0 (Figure 2). Mizushina et al (2010) suggested that synthesized docosyl trans-pcoumarate not only inhibited DNA topoisomerase activity and human cancer cell growth, but may function as an anti-cancer agent [9]. Triancontyl p-coumarate from Bombacopsis glabra plays a role as an inhibitor of snake venom metalloproteinase [10].…”