title: Comparison of cytotoxicity and DNA damage potential induced by ent-kaurene diterpenoids from Isodon plant.
abstract: The cytotoxicity of six ent-kaurene diterpenoids isolated from the leaves of Isodon japonica (Burm.f.) Hara var. galaucocalyx (maxin) Hara was evaluated against three human tumour HepG2, GLC-82 and HL-60 cell lines through SRB assay, and their DNA damage potential (against HepG2 cell line) was assessed by comet assay. Among the six ent-kaurene diterpenoids, Rabdosin B was most cytotoxic, followed by Oridonin, Epinodosin, Rabdosinate, Lasiokaurin and Epinodosinol. All of the six ent-kaurene diterpenoids induced significant DNA damage (p < 0.05) to HepG2 cells in a time- and dose-dependent manner except Lasiokaurin and Eponodosinol at 6 µmol L⁻¹ for 24 h. The structure-activity relationships (SARs) were discussed and it was found that exo-methylene cyclopentanone in the molecular structure was important for maintaining the cytotoxicity and DNA damage potential of the compounds.-OAc group at site C-1 in Lasiokaurin had a higher stereospecific blockade, which made the compound have less cytotoxicity and DNA damage potential than Oridonin (-OH at C-1).
authors.affiliation: College of Life Sciences, Northwest Normal University, Lanzhou, P.R. China. dinglan@nwnu.edu.cn
authors.forename: Lan
authors.initials: L
authors.lastname: Ding
authors.forename: Qiyin
authors.initials: Q
authors.lastname: Zhou
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Shidong
authors.initials: S
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
mesh_terms: D045744:Cell Line, Tumor; D020552:Comet Assay; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D045786:Diterpenes, Kaurane / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D037602:Isodon / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry / Q000379:methods; D013055:Spectrophotometry, Infrared
chemical_list: D045786:Diterpenes, Kaurane; D004247:DNA