title: Apoptosis induction in HL-60 cells and inhibition of topoisomerase II by triterpene celastrol.
abstract: Celastrol, which is a triterpene purified from Celastraceae plants, has anticancer and anti-inflammatory activities. In this study we investigated to clarify whether celastrol can induce apoptosis in a human leukemia HL-60 model system. Celastrol was found to induce apoptosis, and the rank order of the potency of celastrol and its derivatives to induce internucleosomal DNA fragmentation was found to be celastrol>cela-H>>the other derivatives=vehicle control. Many anticancer agents are known to possess the ability to inhibit topoisomerase II, so the inhibitory activities of celastrol and its derivatives on topoisomerase II were also explored. The rank order of the inhibitory activity was found to be celastrol>etoposide>cela-H, indicating that the apoptosis-inducing activities of cela derivatives correspond to their inhibitory activities on topoisomerase II. These data suggested that celastrol may cause its effects such as anticancer activity by the mechanism of apoptosis along with topoisomerase II inhibition.
authors.affiliation: Department of Life Sciences, Faculty of Agriculture, Kagawa University, Miki, Japan. nagase@ag.kagawa-u.ac.jp
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nagase
authors.forename: Jinsei
authors.initials: J
authors.lastname: Oto
authors.forename: Sin
authors.initials: S
authors.lastname: Sugiyama
authors.forename: Kouichi
authors.initials: K
authors.lastname: Yube
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Takaishi
authors.forename: Nobuo
authors.initials: N
authors.lastname: Sakato
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D005047:Etoposide / Q000494:pharmacology; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D053978:Pentacyclic Triterpenes; D013997:Time Factors; D059005:Topoisomerase II Inhibitors; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D053978:Pentacyclic Triterpenes; D059005:Topoisomerase II Inhibitors; D014315:Triterpenes; D005047:Etoposide; C050414:celastrol