2. Academic Validation
  3. Oxidative stress mediated by gyrophoric acid from the lichen Umbilicaria hirsuta affected apoptosis and stress/survival pathways in HeLa cells

Oxidative stress mediated by gyrophoric acid from the lichen Umbilicaria hirsuta affected apoptosis and stress/survival pathways in HeLa cells

  • BMC Complement Altern Med. 2019 Aug 19;19(1):221. doi: 10.1186/s12906-019-2631-4.
Michal Goga 1 2,  Martin Kello 3,  Maria Vilkova 4,  Klaudia Petrova 5,  Martin Backor 6,  Wolfram Adlassnig 7,  Ingeborg Lang 7
Affiliations

Affiliations

  • 1 Core Facility Cell Imaging and Ultrastructure Research, University of Vienna, Althanstrasse 14, 1090, Vienna, Austria. michal.goga@univie.ac.at.
  • 2 Department of Botany, Institute of Biology and Ecology, Faculty of Science, Pavol Jozef Šafárik University, Mánesova 23, 041 67, Košice, Slovakia. michal.goga@univie.ac.at.
  • 3 Department of Pharmacology, Faculty of Medicine, Pavol Jozef Šafárik University, Trieda SNP 1, 040 11, Košice, Slovakia. martin.kello@upjs.sk.
  • 4 Department of NMR Spectroscopy, Institute of Chemistry, Faculty of Science, Pavol Jozef Šafárik University, Moyzesova 11, 040 11, Košice, Slovakia.
  • 5 Department of Pharmacology, Faculty of Medicine, Pavol Jozef Šafárik University, Trieda SNP 1, 040 11, Košice, Slovakia.
  • 6 Department of Botany, Institute of Biology and Ecology, Faculty of Science, Pavol Jozef Šafárik University, Mánesova 23, 041 67, Košice, Slovakia.
  • 7 Core Facility Cell Imaging and Ultrastructure Research, University of Vienna, Althanstrasse 14, 1090, Vienna, Austria.
PMID: 31426865 DOI: 10.1186/s12906-019-2631-4
Abstract

Background: Lichens produce a huge diversity of bioactive compounds with several biological effects. Gyrophoric acid (GA) is found in high concentrations in the common lichen Umbilicaria hirsuta, however evidence for biological activity was limited to anti-proliferative activity described on several Cancer cell lines.

Methods: We developed and validated a new protocol for GA isolation, resulting in a high yield of highly pure GA (validated by HPLC and NMR) in an easy and time saving manner. Anti-proliferative and pro-apoptotic activity, oxygen radicals formation and stress/survival proteins activity changes was study by flow cytometry.

Results: The highly purified GA showed anti-proliferative activity against HeLa (human cervix carcinoma) and other tumor cells. Moreover, GA threated cells showed a significant increase in Caspase-3 activation followed by PARP cleavage, PS externalization and cell cycle changes mediated by oxidative stress. Production of oxygen radicals led to DNA damage and changes in stress/survival pathways activation.

Conclusions: GA treatment on HeLa cells clearly indicates ROS production and Apoptosis as form of occurred cell death. Moreover, DNA damage and changing activity of stress/survival proteins as p38MAPK, ERK1/2 and Akt mediated by GA treatment confirm pro-apoptotic potential. The pharmacological potential of U. hirsuta derived GA is discussed.

Keywords

Akt; Apoptosis; Cervical cancer; Erk1/2; Gyrophoric acid; Oxidative stress; p38MAPK.

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