Usnic acid and atranorin exert selective cytostatic and anti-invasive effects on human prostate and melanoma cancer cells

Galanty, Agnieszka; Koczurkiewicz, Paulina; Wnuk, Dawid; Paw, Milena; Karnas, Elżbieta; Podolak, Irma; Węgrzyn, Maria; Borusiewicz, Magdalena; Madeja, Zbigniew; Czyż, Jarosław; Michalik, Marta

doi:10.1016/j.tiv.2017.01.008

Cited by 50 publications

(37 citation statements)

References 27 publications

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“…Our results provide strong evidence on multiple scales, that apoptosis plays a key role in the activity of GA. This mechanism has already been described for other lichen metabolites including usnic acid, atranorin, diffractaic acid as well as vulpinic acid [4,19,26,27]. Upon exposure to GA caspase-3 activation, PARP cleavage, oxygen radicals production, MMP dissipation, phosphatidyl serin externalisation and cell cycle exhibited consistently significant changes favouring apoptosis.…”

Section: Discussionsupporting

confidence: 58%

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

Goga

Kello

Vilková

et al. 2019

BMC Complement Altern Med

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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.

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Section: Discussionsupporting

confidence: 58%

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

Goga

Kello

Vilková

et al. 2019

BMC Complement Altern Med

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“…UA caused significant decrease in cell viability to 17.2% and 30.7% in MCF7 and LNCaP cells with the IC 50 levels of 71.4 and 77.5 µM, respectively ( P < 0.05). Additionally, selective cytotoxic effect of UA on cancer cells was detected as first mentioned in a recent study . Treatment with 150 µM of UA resulted in reduction of cell viability only to 71.1% and 69.7% in MCF‐10A and RWPE‐1 cells, respectively.…”

Section: Discussionmentioning

confidence: 52%

“…The most interesting is UA produced by Usnea species . UA has been reported in many studies that to be an antiproliferative agent, apoptosis inducer, and a cell cycle arrestor in different cancer cells, such as MCF7, HeLa, HCT‐116, A2780, HT‐29, HepG2, A549, Jurkat, HTB‐140, DU145, and PC‐3. We used MCF7 cells as the HDBC model, LNCaP cells as the HDPC model and the normal cells of the relevant tissues.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, we recently investigated apoptotic and autophagic effects of UA on hepatocellular carcinoma cells (article in revision). However, the cytotoxicity of UA has been also reported to vary depending on the cancer type and cell differentiation . In addition, the possible cytotoxic effect of UA on HDPC cells has not been investigated previously.…”

Section: Introductionmentioning

confidence: 99%

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In vitro cytotoxic and antiproliferative effects of usnic acid on hormone‐dependent breast and prostate cancer cells

Eryılmaz

Eskiler

Egelí

et al. 2018

J Biochem & Molecular Tox

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The aim of the current study was first to investigate cytotoxic activity of usnic acid (UA) on hormone-dependent breast and prostate cancer, and normal cells. Cells were treated with increasing concentrations (25 to 150 µM) of UA for 48 hours and cell viability, quantitative and morphological analysis of cell death, and cell cycle analysis were performed. UA was shown to have selective cytotoxicity on hormone-dependent cancer cells with the IC levels of 71.4 and 77.5 µM for MCF7 and LNCaP cells, respectively. UA induced apoptotic cell death and G0/G1 cell cycle arrest without damaging normal cells. MCF7 cells were more sensitive to UA than LNCaP cells. Our results first revealed that UA is a promising candidate as an alternative agent for hormone-dependent breast and prostate cancers. However, molecular mechanism underlying the UA-mediated cell death in cancer cells should be investigated further.

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“…Furthermore, each of the combined treatment groups induced much more apoptotic cell death and the percentage of G0/G1 phase arrest than either drug alone in cancer cells, in vitro . Recent studies have shown that UA has a molecular inhibitory effect on oncogenic proliferative pathways by regulating related genes and miRNA expressions, apoptosis and cell cycle regulators and the proteins involved in invasive processes on many cancer cells. Tam and/or Enz can regulate cell death by inhibiting hormone receptor activity, ER and AR, in BC and PC cells .…”

Section: Discussionmentioning

confidence: 99%

Synergistic effects of hormone therapy drugs and usnic acid on hormone receptor‐positive breast and prostate cancer cells

Eskiler

Eryılmaz

Yurdacan

et al. 2019

J Biochem & Molecular Tox

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The aim of this study was to investigate the combined effects of usnic acid (UA) and Tamoxifen (Tam) or Enzalutamide (Enz) on hormone receptor‐positive breast and prostate cancer (BC and PC), respectively. The antiproliferative and apoptotic effects of Tam or Enz alone and in combination with UA on MCF7 and LNCaP cancer cells were detected. The results of the WST‐1 assay indicated that UA was a promising anticancer compound that significantly enhanced the effectiveness of hormone therapy drugs compared with each drug alone (combination index < 1). In addition, the combination of UA with Tam or Enz remarkably induced more cell cycle arrest at the G0/G1 phase and apoptosis than only drug‐treated cells (P < 0.01). Consequently, our findings suggest that the combination of UA with Tam or Enz may be a potential therapeutic approach for the treatment of BC and PC and further studies are required to exploit the potential mechanisms of synergistic effects.

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Usnic acid and atranorin exert selective cytostatic and anti-invasive effects on human prostate and melanoma cancer cells

Cited by 50 publications

References 27 publications

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

In vitro cytotoxic and antiproliferative effects of usnic acid on hormone‐dependent breast and prostate cancer cells

Synergistic effects of hormone therapy drugs and usnic acid on hormone receptor‐positive breast and prostate cancer cells

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