, Volume 70, Issue 6, pp 1565–1573 | Cite as

Anti-breast cancer and anti-angiogenic potential of a lichen-derived small-molecule: barbatolic acid

  • Mehmet VarolEmail author
Original Article


Natural products have been used for centuries as the most potent remedies to cure many diseases including cancer diseases. Angiogenesis is defined as the formation of new capillaries from existing vessels and plays a key role in the tumorigenesis process. Barbatolic acid is a little known lichen-derived small-molecule. In the present study, barbatolic acid was isolated from the acetone extract of Bryoria capillaris, and its anti-breast cancer and anti-angiogenic potential was investigated using human umbilical vein endothelial cells (HUVECs), human breast ductal carcinoma (T-47D) and cisplatin-resistant BRCA2-mutated human breast TNM stage IV adenocarcinoma (HCC1428) cells. AlamarBlue™ cell viability, lactate dehydrogenase cellular membrane degradation and PicoGreen™ dsDNA quantitation assays were performed to determine the cytotoxic potential of barbatolic acid. Anti-angiogenic and anti-migratory activities were investigated using endothelial tube formation assay and scratch wound healing assay, respectively. Half maximal inhibitory concentration of barbatolic acid was found to be higher than 100 µM for HUVEC, HCC1428 and T-47D cells. The sub-cytotoxic concentrations such as 25 µM, 50 µM and 100 µM were applied to determine anti-angiogenic and anti-migratory activities. Although the sub-cytotoxic concentrations inhibited endothelial tube formation and cellular migration in a concentration depended manner, barbatolic acid was more effective on the migration of HCC1428 and T-47D breast cancer cells than the migration of HUVECs. Consequently, the findings suggest that barbatolic acid is a promising anti-angiogenic and anti-migratory agent and the underlying activity mechanisms should be investigated by further in vitro and in vivo experiments.


Lichen acid Barbatolic acid Angiogenesis Migration Breast cancer 



I thank, Prof. Ayşen Turk, Prof. Ayşe Tansu Koparal, Assoc. Prof. Mehmet Candan, Assoc. Prof. İlker Avan and Ayşegül Varol from Anadolu University, Eskisehir, Turkey for their contributions and supports, and the Commission of Scientific Research Projects of Anadolu University for the financial supports of the related project (Grant Number 1502F068).

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest regarding the publication of this paper.

Supplementary material

10616_2018_249_MOESM1_ESM.tif (15.6 mb)
Suppl. Figure 1 Images of HUVEC tube formation are shown for 12 h, 24 h and 48 h time points (10X magnification). (TIFF 16009 kb)
10616_2018_249_MOESM2_ESM.tif (12.1 mb)
Suppl. Figure 2 Images of HUVEC scratch wound assays are shown for 0 h, 12 h, 24 h and 48 h time points (10X magnification, scale bar: 200 µm). (TIFF 12408 kb)
10616_2018_249_MOESM3_ESM.tif (12.9 mb)
Suppl. Figure 3 Images of HCC1428 scratch wound assays are shown for 0 h, 12 h, 24 h and 48 h time points (10X magnification, scale bar: 200 µm). (TIFF 13215 kb)
10616_2018_249_MOESM4_ESM.tif (12.2 mb)
Suppl. Figure 4 Images of T-47D scratch wound assays are shown for 0 h, 12 h, 24 h and 48 h time points (10X magnification, scale bar: 200 µm). (TIFF 12510 kb)


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Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.Department of Biology, Faculty of Science, Yunusemre CampusAnadolu UniversityEskisehirTurkey
  2. 2.Department of Molecular Biology and Genetics, Faculty of Science, Kotekli CampusMugla Sitki Kocman UniversityMuglaTurkey

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