Willow bark extract (BNO1455) and its fractions suppress growth and induce apoptosis in human colon and lung cancer cells.
BACKGROUND
Recently, there have been extensive efforts to evaluate the chemopreventive role of substances present in natural products. The aim of this study was to examine the effects of the main groups of compounds (salicylalcohol derivates, flavonoids, proanthocyanidins), and salicin isolated from willow bark extract BNO 1455 on proliferation and apoptosis in human colon and cancer cells.


METHODS
We used human colon cyclooxygenase-2 (COX-2)-positive HT 29 and (COX-2)-negative HCT 116 or lung COX-2 proficient A 549 and low COX-2 expressing SW2 cells. After treatment for 72 h with various concentrations of single substances and acetylsalicylic acid (ASA) as control, inhibition of cell growth and cytotoxicity were measured by colorimetric WST-1 assay and propidium iodide uptake by flow cytometry, respectively. Apoptotic cells were identified by annexin V adhesion using flow cytometry.


RESULTS
Studies on dose-dependent effects of BNO 1455 and its fractions showed anti-proliferative activity of all compounds with 50% maximal growth inhibitory concentrations (GI(50)) between 33.3 and 103.3 microg/ml for flavonoids and proanthocyanidins fractions and 50.0-243.0 microg/ml for salicylalcohol derivates and extract. Apoptosis induction was confirmed by annexin V adherence and analysis of cell morphology based on light scattering characteristics using flow cytometry in all cell lines at GI(50).


CONCLUSIONS
We showed that willow bark extract BNO 1455 an its fractions inhibit the cell growth and promote apoptosis in human colon and lung cancer cell lines irrespective of their COX-selectivity.
Hostanska
Katarina
K
University Hospital Zürich, Department of Internal Medicine, Institute for Complementary Medicine, FGel 102, Rämistrasse 100, CH-8091 Zürich, Switzerland. katarina.hostanska@access.unizh.ch
Jürgenliemk
Guido
G
Abel
Gudrun
G
Nahrstedt
Adolf
A
Saller
Reinhard
R
D017209:Apoptosis / Q000187:drug effects*; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005419:Flavonoids / Q000737:chemistry; D005434:Flow Cytometry; D019073:HT29 Cells / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology*; D008565:Membrane Proteins / Q000378:metabolism; D024301:Plant Bark / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*; D044945:Proanthocyanidins / Q000737:chemistry; D012459:Salicylates / Q000737:chemistry; D032108:Salix; D014407:Tumor Cells, Cultured / Q000187:drug effects
D005419:Flavonoids; D008565:Membrane Proteins; D010936:Plant Extracts; D044945:Proanthocyanidins; D012459:Salicylates; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human