Cytotoxic activities of hypocretenolides from Leontodon hispidus.
The hypocretenolides are a small group of sesquiterpene lactones with an unusual ring structure and are constituents of several species from the tribe Lactuceae of the family Asteraceae. In the present communication we report on the cytotoxic effects of three hypocretenolides (1-3) from Leontodon hispidus on: (a) eight solid-tumor cell lines (A431, HEP2, MCF7, OVCAR3, SK28, SK37, SW872, ZR75-1), tested by a (3)H-thymidine incorporation assay; (b) two different leukemia cell lines (GTB, HL60), measured by a MTT assay; and (c) CD34(+) bone-marrow cells, assessed by scoring the number of colonies derived from primitive and late erythroid progenitors (BFU-E and CFU-E) as well as from granulocytic/macrophagic progenitor cells (CFU-GM). The aglycon 14-hydroxyhypocretenolide (1) exhibited pronounced activities, although its beta-D-glucoside (2) showed no activity, even at the highest concentration tested (2 microM). 14-Hydroxyhypocretenolide-beta-D-glucoside-4',14' '-hydroxyhypocretenoate (3), the ester of the glucoside esterified with the open-chain form of the aglycon, was the most potently cytotoxic substance and proved to be even more active than the positive-control substance helenalin.
Zidorn
C
C
Institut für Pharmakognosie der Universität Innsbruck, A-6020 Innsbruck, Austria.
Stuppner
H
H
Tiefenthaler
M
M
Konwalinka
G
G
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification* / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000187:drug effects; D003114:Colony-Forming Units Assay; D004396:Coloring Agents; D004354:Drug Screening Assays, Antitumor; D004920:Erythropoiesis / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D010946:Plants, Medicinal / Q000737:chemistry*; D012717:Sesquiterpenes / Q000302:isolation & purification* / Q000494:pharmacology; D045789:Sesquiterpenes, Guaiane; D013234:Stem Cells / Q000187:drug effects; D013778:Tetrazolium Salts; D013844:Thiazoles; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D004396:Coloring Agents; D012717:Sesquiterpenes; D045789:Sesquiterpenes, Guaiane; D013778:Tetrazolium Salts; D013844:Thiazoles; C001329:helenalin; C022616:thiazolyl blue