Two cytotoxic sesquiterpene lactones from the leaves of Xanthium strumarium and their in vitro inhibitory activity on farnesyltransferase.
Two xanthanolide sesquiterpene lactones, 8- epi-xanthatin (1) and 8- epi-xanthatin epoxide (2), isolated from the leaves of Xanthium strumarium (Compositae), demonstrated a significant inhibition on the proliferation of cultured human tumor cells, i. e., A549 (non-small cell lung), SK-OV-3 (ovary), SK-MEL-2 (melanoma), XF498 (central nervous system) and HCT-15 (colon) in vitro. They were also found to inhibit the farnesylation process of human lamin-B by farnesyltransferase (FTase), in a dose-dependent manner in vitro (IC 50 value was calculated as 64 and 58 microM, respectively). Due to the relatively high concentrations of 1 and 2 required to obtain an FTase inhibition as compared with those necessary for a cytotoxic effect on tumor cells, it remains unclear whether a relationship between these two activities exists.
Kim
Young Sup
YS
Kim
Jeoung Seob
JS
Park
Sung-Hee
SH
Choi
Sang-Un
SU
Lee
Chong Ock
CO
Kim
Seong-Kie
SK
Kim
Young-Kyoon
YK
Kim
Sung Hoon
SH
Ryu
Shi Yong
SY
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors / Q000187:drug effects*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D051231:Farnesyltranstransferase; D006801:Humans; D020128:Inhibitory Concentration 50; D007783:Lactones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018515:Plant Leaves; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured / Q000187:drug effects; D031210:Xanthium
D000970:Antineoplastic Agents; D007783:Lactones; D010936:Plant Extracts; D012717:Sesquiterpenes; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase