Cytotoxic caffeic acid derivatives from the rhizomes of Cimicifuga heracleifolia.
Activity profiling of the n-BuOH extract from Cimicifuga heracleifolia rhizomes led to the identification of three cytotoxic caffeic acid derivatives, carboxymethyl isoferulate (2), cimicifugic acid A (3), and cimicifugic acid B (4) together with a series of structurally related inactive compounds. The extract was separated by time-based fractionation in a gradient HPLC condition, and cytotoxicity of each fraction was evaluated using HCT116 colon cancer cells in vitro. HPLChyphenated spectroscopy including LC/NMR and LC/PDA/MS provided structural information for phenolic compounds contained in the extract, and further preparative isolation of active compounds 2-4 was achieved by semi-preparative HPLC. Compounds 2-4 showed cytotoxic activity against cancer cells in a dose-dependent manner at the concentrations of 2.5-40 μM, and western blotting analysis showed that these compounds increased expression of cleaved poly ADP ribose polymerase (PARP), a critical apoptosis marker.
College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju, 500-757, Korea.
Soon-Ho
SH
Yim
Hyun Jung
HJ
Kim
Si-Hwan
SH
Park
Jinmi
J
Kim
Darren R
DR
Williams
Da-Woon
DW
Jung
Ik-Soo
IS
Lee
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002109:Caffeic Acids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D031885:Cimicifuga / Q000737:chemistry*; D003110:Colonic Neoplasms / Q000188:drug therapy*; D055808:Drug Discovery; D045325:HCT116 Cells; D006801:Humans; D055670:Medicine, Korean Traditional; D009363:Neoplasm Proteins / Q000378:metabolism; D009994:Osmolar Concentration; D010648:Phenylacetates / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D056910:Republic of Korea; D027343:Rhizome / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D015854:Up-Regulation / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D002109:Caffeic Acids; D009363:Neoplasm Proteins; D010648:Phenylacetates; C578975:carboxymethyl isoferulate; C116092:cimicifugic acid; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases