Abstract
Abstract Protolichesterinic acid (PA) is the major biologically active second metabolite of the lichen Cetraria islandica. PA has anti-proliferative effects on several types of cancer cells, but no effect on normal skin fibroblasts and is an inhibitor of 5- and 12-lipoxygenase (LOX). Usnic acid (UA) (from Cladonia arbuscula) has a wide range of biological activities, e.g. anti-inflammatory, anti-viral and anti-bacterial activity. UA affects pH gradients and inhibits growth and proliferation of several cancer cells. Fatty acid synthase (FASN) is up-regulated in a variety of cancers. Overexpression of human epidermal growth factor receptor 2 (HER2) has been linked to increased translation of FASN. The chemical structure of PA is very similar to the FASN inhibitor, C75. FASN inhibition interacts synergistically with HER2 targeted drugs (e.g. lapatinib) in breast cancer cells and can overcome resistance. Doxorubicin stops DNA replication. The accumulation and distribution of doxorubicin in cells is pH-dependent. Synergistic effects of the lichen compounds and lapatinib or doxorubicin were estimated, using the CalcuSyn software, in the breast cancer cell lines, SK-BR-3 (HER2+, high levels of FASN) T-47D (P53-mutated) and MCF7. Significant synergistic effects were obtained in SK-BR-3 cell line after combined treatment with PA/lapatinib, and in T-47D cells but at higher concentrations. No synergism was seen in MCF7 cells. Treatment with UA/doxorubicin showed marked synergism at all tested concentrations in T-47D cells; none was seen in SK-BR-3 cells. Synergism between a lichen compound and a drug can be related to metabolic effects. Moreover the synergistic effects appear to be cell-type-dependent. Citation Format: Margret Bessadottir, Edda A. Skuladottir, Sindri Baldursson, Sesselja Omarsdottir, Helga M. Ögmundsdottir. Lichen-derived metabolites show synergistic effects in combination with lapatinib and doxorubicin against breast cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 788. doi:10.1158/1538-7445.AM2014-788
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
