Abstract
In this review, we report on the complexity of breast cancer stem cells as key cells in the emergence of a chemoresistant tumor phenotype, and as a result, the appearance of distant metastasis in breast cancer patients. The search for mechanisms that increase sensitivity to chemotherapy and also allow activation of the tumor-specific immune response is of high priority. As we observed throughout this review, natural products isolated or in standardized extracts, such as P2Et or others, could act synergistically, increasing tumor sensitivity to chemotherapy, recovering the tumor microenvironment, and participating in the induction of a specific immune response. This, in turn, would lead to the destruction of cancer stem cells and the decrease in metastasis.Source of Data: Relevant studies were found using the following keywords or medical subject headings (MeSH) in PubMed, and Google Scholar: “immune response” and “polyphenols” and “natural products” and “BCSC” and “therapy” and “metabolism” and “immunogenic cell death.” The focus was primarily on the most recent scientific publication.
Highlights
The antitumor activity of natural products derived from plants is estimated to occur through the combination of various phytochemicals acting synergistically, rather than by isolated molecules, which alone may have greater toxicity and not exert the same activity
Ponti and colleagues were the first to spread Cancer stem cells (CSC) from three breast cancer lesions and from an established breast carcinoma cell line, which grew in vitro in non-adherent cultures [14]. This method allows for studying the properties of breast cancer stem cells (BCSCs) as well as designing therapeutic strategies that target this type of cell [30]
We have recently shown in our laboratory, in a cohort of 78 patients with breast cancer, that those classified as Luminal B and TN who received neoadjuvant therapy before surgery, present an increase in the frequency of BCSC with a CD44+/CD24−/EPCAM+/CD49f+ phenotype together with the expression of aldehyde dehydrogenase (ALDH) compared to healthy donor tissue
Summary
The antitumor activity of natural products derived from plants is estimated to occur through the combination of various phytochemicals acting synergistically, rather than by isolated molecules, which alone may have greater toxicity and not exert the same activity These mixtures have specificity against their molecular targets, which, difficult to identify, are considered drugs in themselves. These molecular targets may be found in events related to the prevention of carcinogenesis, the destruction of tumor cells directly, the modulation of the tumor microenvironment, the activation of the specific anti-tumor immune response, the induction of epigenetic changes, or the improvement of quality of life of the patient [1, 2]. We will focus on the role of these complex extracts on BCSC control through the modulation of energetic metabolisms and immune system activation
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