Sunday, 25 March 2012

Latest Salvestrol Research

Research on Salvestrols is Continuing Around the World

Salvestrols, a unique dietary subclass, exert extensive in vitro anti-invasive and in vivo anti-metastatic activities against cancer.

Much of the current research in cancer therapeutics is aimed at developing drugs to target key molecules for combating tumor cell growth, metastasis, proliferation, or changes in the associated stromal microenvironment. Studies on a wide spectrum of plant secondary metabolites extractable as natural products from fruits, vegetables, teas, spices, and traditional medicinal herbs show that these plant natural products can act as potent anti-inflammatory, antioxidant or anticancer agents. The recent advances in genomics and metabolomics have enabled biologists to better investigate the potential use of immunomodulatory natural products for treatment or control of various cancerous diseasesleading to the identification of salvestrols. The cancer preventive or protective activities of the various immunomodulatory natural products lie in their effects on cellular defenses including detoxifying and antioxidant enzyme systems, and the induction of anti-inflammatory and antitumor or antimetastasis responses, often by targeting specific key transcription factors like nuclear factor kappa B (NF-kappaB), activator protein (AP-1), signal transducers and activators of transcription (STAT) and others. This review presents recent findings and hypotheses on the molecular mechanisms through which various inflammatory activities are linked to tumorigenic processes and the specific immunomodulatory natural products that may suppress inflammation and the associated tumor progression and metastasis. In addition to tumor cells the various associated roles of myeloid-derived suppressor cells, stromal fibroblasts, myofibroblasts, and inflammatory immune cells, and the possible effects of phytomedicines on these cells in the tumor microenvironment is being investigated.

Cancer metastasis refers to the spread of cancer cells from the primary neoplasm to distant sites, where secondary tumors are formed, and is the major cause of death from cancer. Natural phytochemicals containing phenolic compounds have been widely demonstrated to have the capability to prevent cancer metastasis. Among phenolic compounds, flavonoids are a very large subclass, and they are abundant in food and nutraceuticals. A sub-class of flavonoids are called salvestrols. The salvestrols are the important anticancer bioflavonoids. The number of reports demonstrating that flavonoids are an effective natural inhibitor of cancer invasion and metastasis is increasing in the scientific literature. Catechin derivatives are the most studied compounds so far, but genistein, silibinin, quercetin, and anthocyanin have also been widely investigated for their inhibitory activities on invasion and metastasis. Other flavonoids in dietary vegetable foods that are responsible for anti-invasive and anti-metastatic activities of tumors include salvestrol Q40, salvestrol T30, myricetin, salvestrol T55, kaempferol, glycitein, licoricidin, daidzein, and naringenin. To effectively overcome the metastatic cascade, including cell-cell attachment, tissue-barrier degradation, migration, invasion, cell-matrix adhesion, and angiogenesis, it is essential that a bioactive compound prevent tumor cells from metastasizing. This article summarizes the effects of flavonoids on the metastatic cascade and the related proteins, the in vitro anti-invasive activity of flavonoids against cancer cells, and the effects of flavonoids on anti-angiogenic and in vivo anti-metastatic models. The available scientific evidence indicates that salvestrols are a unique dietary phenolics subclass of flavoinoids that exert extensive in vitro anti-invasive and in vivo anti-metastatic activities.

Natural products as anti-invasive and anti-metastatic agents.

Invasion and metastasis, the hallmark of malignant tumor, is the main reason for the clinical death of most cancer patients. Tumor invasion and metastasis are complex, multi-step biochemical processes, which involve cell detachment, invasion, migration, intravasation and circulation, implantation, angiogenesis and proliferation. Therefore, how to prevent tumor metastasis has been the biggest challenge in cancer chemotherapy. In recent years, many natural products have been found to have anti-invasive and anti-metastatic activities. In this paper, these natural compounds are classified as polyphenols, terpenoids, alkaloids, steroids, saccharides, salvestrols, macrolides, amides and their anti-invasive and anti-metastatic activities as well as their biological targets are under investigation.

Plant Salvestrols as anti-invasive cancer agents.

Because invasion is, either directly or via metastasis formation, the main cause of death in cancer patients, development of efficient anti-invasive agents is an important research challenge. We have established a screening program for potentially anti-invasive compounds. The assay is based on organotypic confronting cultures between human invasive cancer cells and a fragment of normal tissue in three dimensions. Anti-invasive agents appeared to be heterogeneous with regard to their chemical nature, but plant alkaloids, salvestrols and some of their synthetic congeners were well represented. Even within this group, active compounds were quite diverse: (+)-catechin, salvestrol T55, xanthohumol and other prenylated chalcones, 3,7-dimethoxyflavone, a pyrazole derivative, an isoxazolylcoumarin and a prenylated desoxybenzoin. The data gathered in this system are now applied in two projects. Firstly, structure-activity relationships are explored with computer models using an artificial neural network approach, based on quantitative structural descriptors. The aim of this study is the prediction and design of optimally efficient anti-invasive compounds. Secondly, the metabolism of orally ingested plant polyphenolics by colonic bacteria is studied in a simulator of the human intestinal microbial ecosystem (SHIME) and in human intervention trials. This method should provide information on the final bioavailability of the active compounds in the human body, with regard to microbial metabolism, and the feasibility of designing pre- or probiotics that increase the generation of active principles for absorption in the gastro-intestinal tract. The final and global aim of all these studies is to predict, synthesize and apply in vivo molecules with an optimal anti-invasive, and hence an anti-metastatic activity against cancer.

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