Oleuropein-Enriched Olive Leaf Extract Affects Calcium Dynamics and Impairs Viability of Malignant Mesothelioma Cells

Our plain-English summary of Oleuropein-Enriched Olive Leaf Extract Affects Calcium Dynamics and Impairs Viability of Malignant Mesothelioma Cells, by C. Marchetti, M. Clericuzio, B. Borghesi, et al (Evidence-based Complementary and Alternative Medicine, 2015).

The study

• Authors: C. Marchetti, M. Clericuzio, B. Borghesi, L. Cornara, S. Ribulla, F. Gosetti, E. Marengo, B. Burlando
• Journal: Evidence-based Complementary and Alternative Medicine
• Published: 2015;2015:908493
• Cited by: 27 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma is a poor prognosis cancer in urgent need of alternative therapies. Oleuropein, the major phenolic of olive tree (Olea europaea L.), is believed to have therapeutic potentials for various diseases, including tumors. We obtained an oleuropein-enriched fraction, consisting of 60% w/w oleuropein, from olive leaves, and assessed its effects on intracellular Ca(2+) and cell viability in mesothelioma cells. Effects of the oleuropein-enriched fraction on Ca(2+) dynamics and cell viability were studied in the REN mesothelioma cell line, using fura-2 microspectrofluorimetry and MTT assay, respectively. Fura-2-loaded cells, transiently exposed to the oleuropein-enriched fraction, showed dose-dependent transient elevations of cytosolic Ca(2+) concentration ([Ca(2+)]i). Application of standard oleuropein and hydroxytyrosol, and of the inhibitor of low-voltage T-type Ca(2+) channels NNC-55-0396, suggested that the effect is mainly due to oleuropein acting through its hydroxytyrosol moiety on T-type Ca(2+) channels. The oleuropein-enriched fraction and standard oleuropein displayed a significant antiproliferative effect, as measured on REN cells by MTT cell viability assay, with IC50 of 22 μg/mL oleuropein. Data suggest that our oleuropein-enriched fraction from olive leaf extract could have pharmacological application in malignant mesothelioma anticancer therapy, possibly by targeting T-type Ca(2+) channels and thereby dysregulating intracellular Ca(2+) dynamics.

In plain English

This was a laboratory study on cells grown in dishes, not on people or animals. It did not study asbestos exposure. The authors made an extract from leaves of the Taggiasca olive cultivar and refined it into a fraction that was 60% oleuropein by weight. Oleuropein is the major phenolic compound of the olive tree. They tested the fraction, along with pure oleuropein and pure hydroxytyrosol, on a malignant mesothelioma cell line called REN.

The fraction and pure oleuropein caused short-lived rises in calcium inside the cells that grew with dose. Removing calcium from the surrounding fluid almost abolished the oleuropein effect. A blocker of T-type calcium channels reduced it. The blocker cut the hydroxytyrosol effect by 80% at 10 micromolar and by 65% at 100 micromolar.

After 48 hours, the concentration that halved cell viability was 22 micrograms per millilitre (95% confidence interval 17 to 29, counted as oleuropein) for the fraction and 25 (20 to 33) for pure oleuropein. That difference was not statistically significant. The authors concluded that the effect suggests a possible use of the fraction in treating mesothelioma.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) cell-culture experiment: preparation and chemical analysis of an olive leaf extract, then calcium-imaging and cell-viability (MTT) assays on mesothelioma cells
• Who was studied: The REN malignant mesothelioma cell line, grown in culture; no human patients or animals were studied
• Exposure: No asbestos exposure was studied. Cells were exposed to an oleuropein-enriched fraction (60% w/w oleuropein) made from leaves of the olive cultivar Taggiasca from Imperia, Italy. Other cells received standard oleuropein, standard hydroxytyrosol, or the green tea compound EGCG (positive control). In the viability tests, exposure lasted 48 hours.
• Main results:
  • In REN cells, the oleuropein-enriched fraction caused transient rises in intracellular calcium that depended on the nominal oleuropein concentration (10 to 30 micromolar).
  • For standard oleuropein, removing calcium from the external solution almost abolished the calcium rise.
  • The T-type calcium channel blocker NNC-55-0396 reversibly reduced the calcium spike caused by 100 micromolar standard oleuropein.
  • NNC-55-0396 inhibited hydroxytyrosol-induced calcium spikes by 80% at 10 micromolar hydroxytyrosol and by 65% at 100 micromolar hydroxytyrosol.
  • The estimated half-maximal effective concentration (EC50) for causing calcium spikes was 12 micromolar for hydroxytyrosol and 53 micromolar for oleuropein. For EGCG it was 69 micromolar.
  • In the 48-hour viability test on REN cells, the fraction had an IC50 of 22 micrograms per mL expressed as oleuropein (95% CI 17 to 29). Standard oleuropein had an IC50 of 25 micrograms per mL (95% CI 20 to 33). The fraction was slightly stronger, but the difference was not statistically significant.
  • The authors restated the fraction's IC50 with its interval: 22 (17 to 29) micrograms per mL in terms of oleuropein.
  • Both the fraction and standard oleuropein were slightly more cytotoxic than EGCG, which had an IC50 of 33 micrograms per mL (95% CI 26 to 41).
  • The authors estimated the IC50 of the whole fraction (not just its oleuropein) at 36.7 micrograms per mL (28.3 to 48.3). They described this as close to the US National Cancer Institute threshold for cytotoxic plant extracts, which is 20 micrograms per mL or lower.
• The authors' conclusion: The authors concluded that oleuropein and its metabolite hydroxytyrosol disrupt calcium dynamics via T-type calcium channels. They stated that this suggests a possible use of the olive leaf oleuropein fraction in treating mesothelioma.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Prognosis.

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