title: Antiproliferative activities of Amaryllidaceae alkaloids from Lycoris radiata targeting DNA topoisomerase I.
abstract: Crude Amaryllidaceae alkaloids (AAs) extracted from Lycoris radiata are reported to exhibit significant anti-cancer activity. However, the specific alkaloids responsible for the pharmacodynamic activity and their targets still remain elusive. In this context, we strived to combine affinity ultrafiltration with topoisomerase I (Top I) as a target enzyme aiming to fish out specific bioactive AAs from Lycoris radiata. 11 AAs from Lycoris radiata were thus screened out, among which hippeastrine (peak 5) with the highest Enrichment factor (EF) against Top I exhibited good dose-dependent inhibition with IC50at 7.25 ± 0.20 μg/mL comparable to camptothecin (positive control) at 6.72 ± 0.23 μg/mL. The molecular docking simulation further indicated the inhibitory mechanism between Top I and hippeastrine. The in vitro antiproliferation assays finally revealed that hippeastrine strongly inhibited the proliferation of HT-29 and Hep G2 cells in an intuitive dose-dependent manner with the IC50values at 3.98 ± 0.29 μg/mL and 11.85 ± 0.20 μg/mL, respectively, and also induced significant cellular morphological changes, which further validated our screening method and the potent antineoplastic effects. Collectively, these results suggested that hippeastrine could be a very promising anticancer candidate for the therapy of cancer in the near future.
authors.affiliation: Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture, Wuhan Botanical Garden, Chinese Academy of Sciences, Wuhan 430074, China.|Graduate University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Gui-Lin
authors.initials: GL
authors.lastname: Chen
authors.affiliation: Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture, Wuhan Botanical Garden, Chinese Academy of Sciences, Wuhan 430074, China.|Graduate University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Yong-Qiang
authors.initials: YQ
authors.lastname: Tian
authors.affiliation: State Key Laboratory for Quality Research in Chinese Medicines, Macau University of Science and Technology, Taipa, Macau.
authors.forename: Jian-Lin
authors.initials: JL
authors.lastname: Wu
authors.affiliation: State Key Laboratory for Quality Research in Chinese Medicines, Macau University of Science and Technology, Taipa, Macau.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture, Wuhan Botanical Garden, Chinese Academy of Sciences, Wuhan 430074, China.|Sino-Africa Joint Research Center, Chinese Academy of Sciences, Wuhan 430074, China.
authors.forename: Ming-Quan
authors.initials: MQ
authors.lastname: Guo
mesh_terms: D047151:Amaryllidaceae Alkaloids / Q000737:chemistry* / Q000302:isolation & purification; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D001665:Binding Sites; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000737:chemistry* / Q000378:metabolism; D057075:Enzyme Assays; D004926:Escherichia coli / Q000737:chemistry / Q000201:enzymology; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism; D019073:HT29 Cells; D056945:Hep G2 Cells; D006801:Humans; D007700:Kinetics; D031426:Lycoris / Q000737:chemistry*; D062105:Molecular Docking Simulation; D018517:Plant Roots / Q000737:chemistry; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D054730:Protein Interaction Domains and Motifs; D013816:Thermodynamics; D059004:Topoisomerase I Inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology
chemical_list: D047151:Amaryllidaceae Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D029968:Escherichia coli Proteins; D059004:Topoisomerase I Inhibitors; C060577:hippeastrine; D004264:DNA Topoisomerases, Type I