Kristin Ingolfsdottir

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 IC₅₀ 4.2 µg/mL and 4.0 µg/mL for (+) and (−)-usnic acid against T-47D, and 5.3 µg/mL and 5.0 µg/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.

Distinguished guest of honour, Gudmundur K. Magnusson, ladies and gentlemen! For us, who are gathered here to honour Dr. Gudmundur K. Magnusson, former Rector and Professor Emeritus, his brilliant career raises feelings of both respect and pride. Dr. Magnusson retired from his position at the University of Iceland on 1 May of this year, but his career has been both diverse and singularly successful. Naturally our feelings are mixed when such a strong leader retires. We will miss him, but at the same time we are thankful for his invaluable efforts on behalf of the University of Iceland. Dr. Magnusson came to the University upon graduation from Uppsala University and studies at the Massachusetts Institute of Technology (MIT) in Boston, USA. He was a lecturer at Uppsala University for a few years, but became a professor at the University of Iceland in 1968, so the University has benefited from his work for close to 40 years. Dr. Magnusson has held many positions of responsibility for the University of Iceland. Immediately in his second year of employment, he became the Dean of the Faculty of Business, as it was known at the time, and later became Rector for a period of six years, from 1979 to 1985. Dr. Magnusson is one of the fathers of formal education in economics in Iceland. The programme in economics at the Faculty of Business was founded on his initiative, and evolved into the founding of the Department of Economics. Dr. Magnusson was also a driving force in the foundation of the Institute of Economic Studies; he was its first director and from the beginning set the course for its operation. The flourishing teaching and research in economics at the University of Iceland is largely thanks to the pioneering efforts of Dr. Magnusson.

Lipoxygenases (LOXs) have been implicated in carcinogenesis in various cancer types. In the current study, three structurally different lichen metabolites, protolichesterinic acid (1), lobaric acid (2) and baeomycesic acid (3) were tested for anti-proliferative effects against 12 different human cancer cell lines. All compounds have known in vitro 5-LOX inhibitory activity, and 1 and 2 also inhibit 12-LOX. The activity of the lichen metabolites was compared to that of a specific 5-LOX inhibitor, zileuton (4). The following cancer cell lines were tested: Capan-1, Capan-2 and PANC-1 (all from pancreas), T47-D (breast), PC-3 (prostate), NCI-H1417 (small cell lung), NIH:OVCAR-3 (ovary), AGS (stomach), WiDr (colorectal), HL-60, K-562 and JURKAT (acute promyelocytic, erythro- and T-cell leukemia, respectively). Compound 1 showed the greatest inhibitory effect against all cell lines, with EC₅₀ ranging from 2.4 - 18.1 μg mL^-1 (7.4 - 55.8 μM), followed by 2, with EC₅₀ of 15.2 - 65.5 μg mL^-1 (33.2 - 143.6 μM). The effects of 3 and 4 were of similar orders of magnitude, with EC₅₀ of 28.7 - >80 μg mL^-1 (76.8 - > 213.9 μM) and 12.9 - > 80 μg mL^-1 (50.4 - > 313.7 μM). The dual 5- and 12-LOX inhibitors 1 and to some extent 2 thus exert significant anti-proliferative effects against a variety of human cancer cell lines, while the selective 5-LOX inhibitors 3 and 4 are considerably less active.

A lichen depsidone derivative, fumarprotocetraric acid, was obtained as the major constituent of Cladonia furcata (Huds.) Schrad. collected in Iceland. In the ¹H NMR spectrum (in DMSO‐d₆) of this compound, the trans double bond proton signals of the fumaryl unit appeared as overlapping singlets. To confirm the presence of a trans double bond in the molecule, fumarprotocetraric acid was treated with triethylamine. The ¹H NMR spectrum of the resultant triethylamine salt displayed a pair of clear doublets with coupling constants of 15.7 Hz, which are characteristic of a trans double bond. Unambiguous ¹H and ¹³C NMR spectral data for both fumarprotocetraric acid and its triethylamine salt were assigned for the first time based on the interpretation of their 2D NMR (HMQC, HMBC and NOESY) spectra. Copyright © 2003 John Wiley & Sons, Ltd.