2-4-3--5--tetrahydroxystilbene and Neoplasms

The Mediterranean diet (MD) is a combination of foods mainly rich in antioxidants and anti-inflammatory nutrients that have been shown to have many health-enhancing effects. Extra-virgin olive oil (EVOO) is an important component of the MD. The importance of EVOO can be attributed to phenolic compounds, represented by phenolic alcohols, hydroxytyrosol, and tyrosol, and to secoiridoids, which include oleocanthal, oleacein, oleuropein, and ligstroside (along with the aglycone and glycosidic derivatives of the latter two). Each secoiridoid has been studied and characterized, and their effects on human health have been documented by several studies. Secoiridoids have antioxidant, anti-inflammatory, and anti-proliferative properties and, therefore, exhibit anti-cancer activity. This review summarizes the most recent findings regarding the pharmacological properties, molecular targets, and action mechanisms of secoiridoids, focusing attention on their preventive and anti-cancer activities. It provides a critical analysis of preclinical, in vitro and in vivo, studies of these natural bioactive compounds used as agents against various human cancers. The prospects for their possible use in human cancer prevention and treatment is also discussed.

Topics: Aldehydes; Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Cyclopentane Monoterpenes; Diet, Mediterranean; Glucosides; Humans; Iridoid Glucosides; Iridoids; Neoplasms; Olive Oil; Phenols; Phenylethyl Alcohol; Pyrans

Cancer is among the leading causes of mortality worldwide. Current cancer therapies are associated with serious side effects, which further damage patients' health. Therefore, the search for new anticancer agents with no toxic effects on normal and healthy cells is of great interest. Recently, we and other groups have demonstrated that oleocanthal (OLC), a phenolic compound from extra virgin olive oil, exhibits antitumor activity in various tumor models. However, the underlying mechanisms and intracellular targets of OLC remain to be completely elucidated. This review summarizes the current advancers concerning the anticancer activity of OLC, with particular emphasis on the molecular signaling pathways modulated by this compound in different tumor cell types. The major mechanisms of action of OLC include modulation of the apoptotic pathway, the HGF/c-Met pathway, and the signal transducer and activator of transcription 3 signaling pathway, among others. Furthermore, OLC has synergistic effects with anticancer drugs in vitro. Also discussed are OLC bioavailability and its concentration in olive oil. Data summarized here will represent a database for more extensive studies aimed at providing information on molecular mechanisms against cancer induced by OLC.

Topics: Aldehydes; Antineoplastic Agents; Cyclopentane Monoterpenes; Humans; Neoplasms; Olive Oil; Phenols; Signal Transduction

Oleocanthal is a minor constituent of olive oil with strong anti-inflammatory activities. Since the pathogenesis of many chronic diseases involves inflammatory and oxidative components, oleocanthal is a promising agent to prevent these conditions. This review aimed to summarise the current beneficial health effects of oleocanthal and the molecular basis of its biological actions. The anti-inflammatory, antioxidative, antimicrobial, anticancer and neuroprotective activities of oleocanthal have been examined by previous studies. Of these, studies on the anticancer effects have been the most extensive. Oleocanthal was reported to suppress melanoma, breast, liver, and colon cancer cells. Neurological studies focused on the effects of oleocanthal against Alzheimer’s disease. Oleocanthal improved clearance of the amyloid beta protein from neurons and reduced the inflammation of astrocytes. Despite the positive results, validation of the biological effects of oleocanthal in animal disease models is limited and should be emphasized in the future. As a conclusion, oleocanthal may act together with other bioactive compounds in olive oil to achieve its therapeutic potential. The use of oleocanthal alone as a single therapeutic measure awaits validation from future studies.

Topics: Aldehydes; Alzheimer Disease; Amyloid beta-Peptides; Animals; Anti-Infective Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Astrocytes; Cell Line, Tumor; Cyclopentane Monoterpenes; Disease Models, Animal; Humans; Inflammation; Neoplasms; Neurons; Neuroprotective Agents; Olive Oil; Phenols

The broad number of health benefits which can be obtained from the long-term consumption of olive oil are attributed mainly to its phenolic fraction. Many olive oil phenolics have been studied deeply since their discovery due to their bioactivity properties, such as Hydroxytyrosol. Similarly, in the last decade, the special attention of researchers has been addressed to Oleocanthal (OC). This olive oil phenolic compound has recently emerged as a potential therapeutic agent against a variety of diseases, including cancer, inflammation, and neurodegenerative and cardiovascular diseases. Recently, different underlying mechanisms of OC against these diseases have been explored. This review summarizes the current literature on OC to date, and focuses on its promising bioactivities against different disease-targets.

Topics: Aldehydes; Biological Products; Cardiovascular Diseases; Cyclopentane Monoterpenes; Humans; Inflammation; Neoplasms; Neurodegenerative Diseases; Olive Oil; Phenols

Chronic inflammation is a critical factor in the pathogenesis of many inflammatory disease states including cardiovascular disease, cancer, diabetes, degenerative joint diseases and neurodegenerative diseases. Chronic inflammatory states are poorly understood, however it is known that dietary habits can evoke or attenuate inflammatory responses. Popular methods to deal with inflammation and its associated symptoms involve the use of non steroidal anti-inflammatory drugs, however the use of these drugs are associated with severe side effects. Therefore, investigations concerned with natural methods of inflammatory control are warranted. A traditional Mediterranean diet has been shown to confer some protection against the pathology of chronic diseases through the attenuation of pro-inflammatory mediators and this has been partially attributed to the high intake of virgin olive oil accompanying this dietary regime. Virgin olive oil contains numerous phenolic compounds that exert potent anti-inflammatory actions. Of interest to this paper is the recently discovered phenolic compound oleocanthal. Oleocanthal is contained in virgin olive oil and possesses similar anti-inflammatory properties to ibuprofen. This pharmacological similarity has provoked interest in oleocanthal and the few studies conducted thus far have verified its anti-inflammatory and potential therapeutic actions. A review of the health benefits of the Mediterranean diet and anti-inflammatory properties of virgin olive oil is presented with the additional emphasis on the pharmacological and anti-inflammatory properties of the phenolic compound oleocanthal.

Topics: Aldehydes; Animals; Anti-Inflammatory Agents; Biomarkers; Cardiovascular Diseases; Cyclopentane Monoterpenes; Diet, Mediterranean; Humans; Inflammation; Models, Immunological; Neoplasms; Olive Oil; Phenols; Plant Oils; Signal Transduction

Olive oil phenols (OOPs) are associated with the prevention of many human cancers. Some of these have been shown to inhibit cell proliferation and induce apoptosis. However, no systematic comparative study exists for all the investigated compounds under the same conditions, due to difficulties in their isolation or synthesis. Herein are presented innovative methods for large-scale selective extraction of six major secoiridoids from olive oil or leaves enabling their detailed investigation. The cytotoxic/antiproliferative bioactivity of these six compounds was evaluated on sixteen human cancer cell lines originating from eight different tissues. Cell viability with half-maximal effective concentrations (EC50) was evaluated after 72 h treatments. Antiproliferative and pro-apoptotic effects were also assessed for the most bioactive compounds (EC50 ≤ 50 μM). Oleocanthal (1) showed the strongest antiproliferative/cytotoxic activity in most cancer cell lines (EC50: 9−20 μM). The relative effectiveness of the six OOPs was: oleocanthal (1) > oleuropein aglycone (3a,b) > ligstroside aglycone (4a,b) > oleacein (2) > oleomissional (6a,b,c) > oleocanthalic acid (7). This is the first detailed study comparing the bioactivity of six OOPs in such a wide array of cancer cell lines, providing a reference for their relative antiproliferative/cytotoxic effect in the investigated cancers.

Topics: Antineoplastic Agents; Cell Line; Humans; Iridoids; Neoplasms; Olea; Olive Oil