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.

Highlights

  • Breast cancer (BC) is a disease that features several morphological aspects, different therapeutic responses, and variable clinical outcomes

  • To control the competitive inhibition caused by the coproduct glucose (Ranieri et al, 2018), we studied the effect of glucose amount in contact with the enzyme, and its removal by UF (Table 1)

  • The integrated membrane system was composed of an membrane bioreactor (MBR), where the oleuropein aglycone (OLA) was produced, and by a membrane emulsification (ME) process, where the compound was extracted in a volatile green organic solvent

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Summary

Introduction

Breast cancer (BC) is a disease that features several morphological aspects, different therapeutic responses, and variable clinical outcomes. In industrialized countries, it represents the most common cause of death in women (Ferlay et al, 2015; Kohler et al, 2015). Current therapeutic cancer treatments are based on various methods including surgical removal, radiotherapy, chemotherapy, biological therapy, and hormone therapy. The side effects of these therapies are innumerable, and some of them are related to the cytotoxic activity of drugs that act indistinctly both on cancer cells and on healthy ones. The severe side effects of these therapies, such as nausea, vomiting, diarrhea, mucositis, and myelosuppression decrease the quality of life of the patients (Sharma et al, 2005). Increasing instances of tumors with resistance to current therapeutic compounds has become a problematic issue, which has pushed research toward new anticancer agents (Vidal et al, 2014; Carnero et al, 2016)

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