title: Anti-proliferative activities of terpenoids isolated from Alisma orientalis and their structure-activity relationships.
abstract: This study aimed to isolate terpenoids from Alisma orientalis (Sam.) Juzep. and elucidate their antiproliferative activities, as well as structure-activity relationships. Fourteen protostane-type triterpenoids were isolated from the rhizome of A. orientalis. Among these triterpenoids, alisol A (1), alisol A 24-acetate (2), alisol B (3), alisol B 23-acetate (4), and alisol G (8) presented inhibitory effects on cancer cell lines tested. Compounds 3 and 4 showed the highest potential; IC50 values for HepG2, MDA-MB-231, and MCF-7 cells were 16.28, 14.47, and 6.66 μM for 3 and 18.01, 15.97, and 13.56 μM for 4, respectively. Based on these results, we concluded that the degree of C-16 oxidation and the double bond between C-13 and C-17 may be significant in anti-proliferative activities. Further study showed that 3 and 4 effectively induced apoptosis, as confirmed by flow cytometry. Increased intracellular calcium concentration and endoplasmic reticulum stress were detected after treatment with 4 in HepG2 cells. Although compounds 1 and 2 induced minimal apoptosis, they evidently delayed the G2/M phase in HepG2 cells. Further study showed that 1-4 also enhanced LC3II expression, indicating autophagy is occured.
authors.forename: Wen
authors.initials: W
authors.lastname: Xu
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.forename: Jian-Fang
authors.initials: JF
authors.lastname: Qiu
authors.forename: Shui-Sheng
authors.initials: SS
authors.lastname: Wu
authors.forename: Ming-Qing
authors.initials: MQ
authors.lastname: Huang
authors.forename: Li-Gen
authors.initials: LG
authors.lastname: Lin
authors.forename: Qing-Wen
authors.initials: QW
authors.lastname: Zhang
authors.forename: Xiu-Ping
authors.initials: XP
authors.lastname: Chen
authors.affiliation: College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China. hmq1115@126.com.
authors.forename: Jin-Jian
authors.initials: JJ
authors.lastname: Lu
mesh_terms: D034902:Alisma / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002783:Cholestenones / Q000737:chemistry / Q000494:pharmacology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D010936:Plant Extracts / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013729:Terpenes / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D002783:Cholestenones; D010936:Plant Extracts; D013729:Terpenes; C457233:alisol A 24-acetate; C526957:alisol B 23-acetate; C457232:alisol B; C000050:alisol A; D002118:Calcium