Cytotoxic activity of polyacetylenes and polyenes isolated from roots of Echinacea pallida.
OBJECTIVE
The n-hexane extracts of the roots of three medicinally used Echinacea species exhibited cytotoxic activity on human cancer cell lines, with Echinacea pallida found to be the most cytotoxic. Acetylenes are present in E. pallida lipophilic extracts but essentially absent in extracts from the other two species. In the present study, the cytotoxic effects of five compounds, two polyacetylenes (namely, 8-hydroxy-pentadeca-(9E)-ene-11,13-diyn-2-one (1) and pentadeca-(9E)-ene-11,13-diyne-2,8-dione (3)) and three polyenes (namely, 8-hydroxy-pentadeca-(9E,13Z)-dien-11-yn-2-one (2), pentadeca-(9E,13Z)-dien-11-yne-2,8-dione (4) and pentadeca-(8Z,13Z)-dien-11-yn-2-one (5)), isolated from the n-hexane extract of E. pallida roots by bioassay-guided fractionation, were investigated and the potential bioavailability of these compounds in the extract was studied.


METHODS
Cytotoxic effects were assessed on human pancreatic MIA PaCa-2 and colonic COLO320 cancer cell lines. Cell viability was evaluated by the WST-1 assay and apoptotic cell death by the cytosolic internucleosomal DNA enrichment and the caspase 3/7 activity tests. Caco-2 cell monolayers were used to assess the potential bioavailability of the acetylenes.


RESULTS
The five compounds exhibited concentration-dependent cytotoxicity in both cell types, with a greater potency in the colonic cancer cells. Apoptotic cell death was found to be involved in the cytotoxic effect of the most active, compound 5. Compounds 2 and 5 were found to cross the Caco-2 monolayer with apparent permeabilities above 10 x 10(-6) cm s(-1).


CONCLUSIONS
Compounds isolated from n-hexane extracts of E. pallida roots have a direct cytotoxicity on cancer cells and good potential for absorption in humans when taken orally.
Chicca
A
A
Department of Psychiatry, Neurobiology, Pharmacology and Biotechnology, University of Pisa, Pisa, Italy.
Pellati
F
F
Adinolfi
B
B
Matthias
A
A
Massarelli
I
I
Benvenuti
S
S
Martinotti
E
E
Bianucci
A M
AM
Bone
K
K
Lehmann
R
R
Nieri
P
P
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000302:isolation & purification / Q000493:pharmacokinetics; D017209:Apoptosis / Q000187:drug effects; D001681:Biological Assay; D001682:Biological Availability; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D020900:Echinacea / Q000737:chemistry*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy; D010539:Permeability; D010936:Plant Extracts / Q000008:administration & dosage* / Q000302:isolation & purification / Q000493:pharmacokinetics; D011090:Polyenes / Q000008:administration & dosage* / Q000302:isolation & purification / Q000493:pharmacokinetics; D053279:Polyynes / Q000008:administration & dosage* / Q000302:isolation & purification / Q000493:pharmacokinetics
D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D011090:Polyenes; D053279:Polyynes