Dataset Information

Production of Plant-Derived Oleuropein Aglycone by a Combined Membrane Process and Evaluation of Its Breast Anticancer Properties.

ABSTRACT: Natural products and herbal therapies represent a thriving field of research, but methods for the production of plant-derived compounds with a significative biological activity by synthetic methods are required. Conventional commercial production by chemical synthesis or solvent extraction is not yet sustainable and economical because toxic solvents are used, the process involves many steps, and there is generally a low amount of the product produced, which is often mixed with other or similar by-products. For this reason, alternative, sustainable, greener, and more efficient processes are required. Membrane processes are recognized worldwide as green technologies since they promote waste minimization, material diversity, efficient separation, energy saving, process intensification, and integration. This article describes the production, characterization, and utilization of bioactive compounds derived from renewable waste material (olive leaves) as drug candidates in breast cancer (BC) treatment. In particular, an integrated membrane process [composed by a membrane bioreactor (MBR) and a membrane emulsification (ME) system] was developed to produce a purified non-commercially available phytotherapic compound: the oleuropein aglycone (OLA). This method achieves a 93% conversion of the substrate (oleuropein) and enables the extraction of the compound of interest with 90% efficiency in sustainable conditions. The bioderived compound exercised pro-apoptotic and antiproliferative activities against MDA-MB-231 and Tamoxifen-resistant MCF-7 (MCF-7/TR) cells, suggesting it as a potential agent for the treatment of breast cancer including hormonal resistance therapies.

SUBMITTER: Mazzei R

PROVIDER: S-EPMC7551858 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Production of Plant-Derived Oleuropein Aglycone by a Combined Membrane Process and Evaluation of Its Breast Anticancer Properties.

Mazzei Rosalinda R Piacentini Emma E Nardi Monica M Poerio Teresa T Bazzarelli Fabio F Procopio Antonio A Di Gioia Maria Luisa ML Rizza Pietro P Ceraldi Rosangela R Morelli Catia C Giorno Lidietta L Pellegrino Michele M

Frontiers in bioengineering and biotechnology 20200929

Natural products and herbal therapies represent a thriving field of research, but methods for the production of plant-derived compounds with a significative biological activity by synthetic methods are required. Conventional commercial production by chemical synthesis or solvent extraction is not yet sustainable and economical because toxic solvents are used, the process involves many steps, and there is generally a low amount of the product produced, which is often mixed with other or similar b ...[more]

PMID: 33117773

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Project description:BackgroundThe fungal natural products illudin S and M have been investigated as precursors for the development of semisynthetic anticancer agents such as Irofulven (illudin S derivative) which is currently in phase II clinical trials. Recently, illudin M derivatives have shown improved in vitro selectivity towards cancer cells encouraging further investigation. This requires a stable supply of the precursor which is produced by Basidiomycota of the genus Omphalotus. We have recently reported a robust shake flask process for the production of gram quantities of illudin M from Omphalotus nidiformis aiming to transfer that process into stirred tank bioreactors, which can be used in a commercial production set-up. However, process transfer across different systems is not straightforward and particularly challenging when the producer is morphologically complex. There are only a few reports that address the development of bioprocesses for the production of compounds from Basidiomycota as these organisms have not been extensively studied because of their complex life cycles and often are difficult to cultivate under laboratory conditions.ResultsThe recently developed shake flask process delivering stable titers of ~ 940 mg L-1 of illudin M was investigated using off-gas analysis to identify critical parameters which facilitated the transfer from shaken into stirred tank bioreactors. Comparable titers to the shake flask process were achieved in 2 L stirred tank bioreactors (1.5 L working volume) by controlling growth of biomass with a carefully timed pH-shift combined with an improved precursor-feeding strategy. A scale-up experiment in a 15 L bioreactor (10 L working volume), resembling the process at 1.5 L resulted in 523 mg L-1 and is the starting point for optimization of the identified parameters at that scale.ConclusionBy identifying and controlling key process parameters, the production process for illudin M was transferred from shake flasks into 2 L stirred tank bioreactors reaching a comparable titer (> 900 mg L-1), which is significantly higher than any previously reported. The insights obtained from 10 L scale pave the way towards further scale-up studies that will enable a sustainable supply of illudin M to support preclinical and clinical development programs.

Dataset Information

Production of Plant-Derived Oleuropein Aglycone by a Combined Membrane Process and Evaluation of Its Breast Anticancer Properties.

Publications

Production of Plant-Derived Oleuropein Aglycone by a Combined Membrane Process and Evaluation of Its Breast Anticancer Properties.

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