Cristina Sánchez-Quesada

Antioxidant, Antiproliferative, and Pro-apoptotic Capacities of Pentacyclic Triterpenes Found in the Skin of Olives on MCF-7 Human Breast Cancer Cells and Their Effects on DNA Damage

This research aimed to investigate erythrodiol, uvaol, oleanolic acid, and maslinic acid scavenging capacities and their effects on cytotoxicity, cell proliferation, cell cycle, apoptosis, reactive oxygen species (ROS) level, and oxidative DNA damage on human MCF-7 breast cancer cell line. The results showed that erythrodiol, uvaol, and oleanolic acid have a significant cytotoxic effect and inhibit proliferation in a dose- and time-dependent manner. At 100 μM, erythrodiol growth inhibition occurred through apoptosis, with the observation of important ROS production and DNA damage, whereas uvaol and oleanolic acid growth inhibition involved cell cycle arrest. Moreover, although all tested triterpenes did not show free radical scavenging activity using ABTS and DPPH assays, they protected against oxidative DNA damage at the concentration 10 μM. Uvaol and oleanolic and maslinic acids, tested at 10 and 100 μM, also reduced intracellular ROS level and prevented H(2)O(2)-induced oxidative injury. Overall, the results suggest that tested triterpenes may have the potential to provide significant natural defense against human breast cancer.

Squalene protects against oxidative DNA damage in MCF10A human mammary epithelial cells but not in MCF7 and MDA-MB-231 human breast cancer cells

Until now, very little has been known about the antioxidant capacity of squalene and its effect on human breast tumourigenesis. In the present work, we investigated squalenes scavenging properties and its effect on cell proliferation, cell cycle profile, apoptosis, reactive oxygen species (ROS) level and oxidative DNA damage, using human breast cell lines. Our results showed that squalene neither possesses scavenging activity nor significantly alters cell proliferation rates, the cell cycle profile or cell apoptosis in human mammary epithelial cells (MCF10A), minimally invasive (MDA-MB-231) breast cancer cells, and highly invasive (MCF7) breast cancer cells. However, we found that squalene did exert the following effects on MCF10A epithelial cells in a dose-dependent manner: (a) it decreased intracellular ROS level, (b) it prevented H(2)O(2)-induced oxidative injury, and (c) it protected against oxidative DNA damage. Interestingly, squalene did not exert these effects on MCF7 and MDA-MB-231 cancer cells. Therefore, our data suggest that squalene, found in high amounts in virgin olive oils, could be partially responsible for the lower incidence of breast cancer in populations that consume the Mediterranean diet due to its protective activity against oxidative DNA damage in normal mammary cells.

Bioactive properties of the main triterpenes found in olives, virgin olive oil, and leaves of Olea europaea.

Oleanolic acid, maslinic acid, uvaol, and erythrodiol are the main triterpenes present in olives, olive tree leaves, and virgin olive oil. Their concentration in virgin olive oil depends on the quality of the olive oil and the variety of the olive tree. These triterpenes are described to present different properties, such as antitumoral activity, cardioprotective activity, anti-inflammatory activity, and antioxidant protection. Olive oil triterpenes are a natural source of antioxidants that could be useful compounds for the prevention of multiple diseases related to cell oxidative damage. However, special attention has to be paid to the concentrations used, because higher concentration may lead to cytotoxic or biphasic effects. This work explores all of the bioactive properties so far described for the main triterpenes present in virgin olive oil.

Phytoestrogen (+)-pinoresinol exerts antitumor activity in breast cancer cells with different oestrogen receptor statuses.

BackgroundConsumption of virgin olive oil (VOO) has been associated with a low breast cancer incidence. Pinoresinol is a phytoestrogen that is typically found in VOO. Considering the role of oestrogen in breast cancer development and progression, we investigated the potential antitumor activity of pinoresinol in breast cancer cells.MethodsTo address this question, we treated MDA-MB-231 (oestrogen receptor [ER] negative) and MCF7 (ER+) human breast tumour cells and MCF10A human mammary epithelial cells (ER-) with different concentrations of pinoresinol. The cytotoxic activity, cell proliferation, cell cycle profile, apoptosis induction, reactive oxygen species production and DNA damage were assessed.ResultsPinoresinol showed cytotoxic, anti-proliferative and pro-oxidant activity in human breast tumour cells, independent of their oestrogen receptor status. In addition, pinoresinol exerted antioxidant activity and prevented DNA damage associated with oxidative stress in human mammary epithelial cells.ConclusionsOverall, the results suggest that pinoresinol may have antitumor activity in human breast cancer cells independently of oestrogen receptor status. Furthermore, the results show that the pinoresinol has the typical characteristics of a chemopreventive compound.

Oleanolic Acid, a Compound Present in Grapes and Olives, Protects against Genotoxicity in Human Mammary Epithelial Cells

Oleanolic acid (AO) and maslinic acid (MA) are constituents of the skins of different fruits, including olives and white or red grapes. Although both compounds are known to have beneficial properties against different types of cancers, thus far, there are no studies about their chemopreventive effects in human breast cancer. Thus, we sought to elucidate whether both compounds possess chemopreventive activity. Two cell lines of human breast cancer cells and one noncancerous human mammary epithelial cells were used to determine the effects of OA and MA. The results showed that OA inhibited the proliferation and increased the oxidative stress of highly invasive cells. Additionally, OA decreased oxidative stress and oxidative damage to the DNA in human mammary epithelial cells. These results suggest that OA could act as a chemopreventive agent in human breast cancer and could inhibit the proliferation of highly invasive breast cancer cells.

Maslinic Acid enhances signals for the recruitment of macrophages and their differentiation to m1 state.

The inflammatory process is involved in the genesis and evolution of different diseases like obesity, cardiovascular disease, and cancer. Macrophages play a central role in inflammation. In addition, they can regulate some stages of cancer development. Macrophages can polarize into M1 or M2 functional phenotype depending on the cytokines present in the tissue microenvironment. On the other hand, triterpenes found in virgin olive oil are described to present different properties, such as antitumoral and anti-inflammatory activity. The present study was designed to elucidate if the four major triterpenes found in virgin olive oil (oleanolic acid, maslinic acid, uvaol, and erythrodiol) are able to enhance M1 macrophage response which represents an important defense mechanism against cancer. Our results indicated that maslinic acid modulated the inflammatory response by enhancing the production of IL-8, IL-1α, and IL-1β; it promoted M1 response through the synthesis of IFN-γ; and finally it did not modify significantly the levels of NFκβ or NO. Overall, our results showed that maslinic acid could prevent chronic inflammation, which represents a crucial step in the development of some cancers.

Molecular Aspects of Squalene and Implications for Olive Oil and the Mediterranean Diet

Virgin olive oil is considered a key component of the Mediterranean diet, being the main source of dietary lipids. Squalene is a terpenoid hydrocarbon found at high concentration in virgin olive oils; it represents their main minor component. Thus squalene is a naturally occurring lipid component consumed by humans as an integral part of a healthy diet. It is recognized as a functional compound of high importance because of its beneficial effects on human health. It could be partially responsible to the health benefits attributed to virgin olive oil. Squalene has several beneficial properties: it is a natural antioxidant, it decreases serum cholesterol concentrations, and it possesses photoprotective, tumor-protective, and cardioprotective properties. Consequently, adequate intake of virgin olive oil provides a continuous supply of squalene, which is considered a remarkable bioactive substance with several interesting biological activities, and it might be sufficient to achieve the health benefits described above.

Squalene Stimulates a Key Innate Immune Cell to Foster Wound Healing and Tissue Repair

Anti-inflammatory effects of virgin olive oil (VOO) have been described recently, along with its wound healing effect. One of the main minor compounds found in VOO is squalene (SQ), which also possesses preventive effects against skin damage and anti-inflammatory properties. The inflammatory response is involved in wound healing and manages the whole process by macrophages, among others, as the main innate cells with a critical role in the promotion and resolution of inflammation for tissue repair. Because of that, this work is claimed to describe the role that squalene exerts in the immunomodulation of M1 proinflammatory macrophages, which are the first cells implicate in recent injuries. Pro- and anti-inflammatory cytokines were analysed using TPH1 cell experimental model. SQ induced an increase in the synthesis of anti-inflammatory cytokines, such as IL-10, IL-13, and IL-4, and a decrease in proinflammatory signals, such as TNF-α and NF-κB in M1 proinflammatory macrophages. Furthermore, SQ enhanced remodelling and repairing signals (TIMP-2) and recruitment signals of eosinophils and neutrophils, responsible for phagocytosis processes. These results suggest that SQ is able to promote wound healing by driving macrophage response in inflammation. Therefore, squalene could be useful at the resolution stage of wound healing.

Additional file 1: of Phytoestrogen (+)-pinoresinol exerts antitumor activity in breast cancer cells with different oestrogen receptor statuses

Representative flow cytometry analysis of the cell cycle of MDA-MB-231, MCF7 and MCF10A cells after treatment with (+)-pinoresinol. (DOCX 205 kb)