Cellular mechanisms of the anticancer effects of the lichen compound usnic acid.
The lichen compound usnic acid is used for its antimicrobial activities in cosmetic products and is also a component of slimming agents. Its effect against cancer cells was first noted over 30 years ago. In this study possible mechanisms of this effect were investigated using two human cell lines, the breast cancer cell line T-47D and the pancreatic cancer cell line Capan-2. Pure (+)-usnic acid from CLADONIA ARBUSCULA and (-)-usnic acid from ALECTORIA OCHROLEUCA were shown to be equally effective inhibitors of DNA synthesis, with IC (50) 4.2 microg/mL and 4.0 microg/mL for (+) and (-)-usnic acid against T-47D, and 5.3 microg/mL and 5.0 microg/mL against Capan-2, respectively. Flow cytometric analysis confirmed the inhibited entry into the S-phase and showed reduction in cell size. Classical apoptosis, as assessed by TUNEL staining, was not observed. Necrosis, measured by LDH release, was seen only in Capan-2 after exposure for 48 hours. Staining with the mitochondrial dye JC-1 demonstrated dose-dependent loss of mitochondrial membrane potential following treatment with usnic acid in both cell lines. In conclusion, usnic acid had a marked inhibitory effect on growth and proliferation of two different human cancer cell lines and led to loss of mitochondrial membrane potential. Cell survival was little affected; late necrosis was seen in one of the cell lines. No difference was noted between the two enantiomers.
Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavik, Iceland.
Eydis
E
Einarsdóttir
Judith
J
Groeneweg
Guethrún G
GG
Björnsdóttir
Guethleif
G
Harethardottir
Sesselja
S
Omarsdóttir
Kristín
K
Ingólfsdóttir
Helga M
HM
Ogmundsdóttir
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D001562:Benzimidazoles; D001572:Benzofurans / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002232:Carbocyanines; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D020128:Inhibitory Concentration 50; D008011:Lichens / Q000737:chemistry*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009336:Necrosis; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use
D000972:Antineoplastic Agents, Phytogenic; D001562:Benzimidazoles; D001572:Benzofurans; D002232:Carbocyanines; D010936:Plant Extracts; C073339:usnic acid; C068624:5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine; D004247:DNA