Eine immer wiederkehrende Frage ist, welchen wissenschaftlichen Nachweis es denn gibt, dass Flavonoide wirklich notwendig für eine erfolgreiche Behandlung von Krebserkrankungen sind. Hierzu hänge ich zwei aktuelle Literaturstellen zur onkogenen Transformation von PI-3K (Phosphoinositol 3-kinase) - induziertem PIP3 (Inositol 3,4,5 phopshate) an sowie der Flavonoid-bedingten Unterdrückung von PIP3. In einer dritten Veröffentlichung verweise ich auf die preventive Fähigkeit von Flavonoiden die Krebsentstehung zu verhindern.
Two current scientific reports explain why treatments combining flavonoids are a necessary requirement to treat cancers successfully. Flavonoids inhibit synthesis of PI-3K (Phosphoinositol 3-kinase) induced PIP3 (Inositol 3,4,5 phosphate) that is an essential component for oncogenesis. A third report illustrates that dietary flavonoids can also be used as cancer preventive agents.
Requirement of phosphatidylinositol(3,4,5)trisphosphate in phosphatidylinositol 3-kinase-induced oncogenic transformation.
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Abstract
Phosphatidylinositol 3-kinases (PI3K) are divided into three classes, which differ in their substrates and products. Class I generates the inositol phospholipids PI(3)P, PI(3,4)P2, and PI(3,4,5)P3 referred as PIP, PIP2, and PIP3, respectively. Class II produces PIP and PIP2, and class III generates only PIP. Substrate and product differences of the three classes are determined by the activation loops of their catalytic domains. Substitution of the class I activation loop with either class II or III activation loop results in a corresponding change of substrate preference and product restriction. We have evaluated such activation loop substitutions to show that oncogenic activity of class I PI3K is linked to the ability to produce PIP3. We further show that reduction of cellular PIP3 levels by the 5'-phosphatase PIPP interferes with PI3K-induced oncogenic transformation. PIPP also attenuates signaling through Akt and target of rapamycin. Class III PI3K fails to induce oncogenic transformation. Likewise, a constitutively membrane-bound class I PI3K mutant retaining only the protein kinase is unable to induce transformation. We conclude that PIP3 is an essential component of PI3K-mediated oncogenesis and that inability to generate PIP3 abolishes oncogenic potential.
- PMID: 19584261
Inhibitory Activity of Flavonoids against Class I Phosphatidylinositol 3-Kinase Isoforms.
School of Pharmaceutical Sciences and Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China. kongdexin@tijmu.edu.cn.
Abstract
Class I PI3 Kinase (PI3K) phosphorylates phosphatidylinositol 4,5-bisphophate (PIP2) to generate the second messenger phosphatidylinositol 3,4,5-trisphosphate (PIP3) and therefore plays an important role in fundamental cellular responses such as proliferation. There are four isoforms of class I PI3K which are known to have different functions and relate to various diseases such as cancer and inflammation. Flavonoids are abundant in fruits, vegetables and plant-derived beverages such as tea. So far, various pharmacological effects of flavonoids have been reported. We previously reported that the flavonoid baicalein exhibits potent PI3K-inhibitory activity. Recently we examined the inhibitory activity of eighteen flavonoids against PI3Ka by using an in vitro homogenous time resolved fluorescence (HTRF) kinase assay, and deduced their structure-activity relationships by comparing the activities of the analogues. Our result suggests that the number of hydroxyl groups in the A and B rings might promote the activity, while loss of C2-C3 double bond might reduce the activity. Furthermore, the activity against 4 class I PI3K isoforms of some selected flavonoids was investigated, and the results indicate that the flavonoids seem to exhibit more potent activity on PI3Ka and d isoforms compared with that on PI3Kb and g isoforms.
Dietary flavonoids as cancer prevention agents.
Department of Stomatology, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Abstract
Dietary agents identified from fruits and vegetables contribute to keeping balanced cell proliferation and preventing cell carcinogenesis. Dietary flavonoids, combined with other components such as various vitamins, play an important role in cancer prevention. Flavonoids act on reactive oxygen species, cell signal transduction pathways related to cellular proliferation, apoptosis, and angiogenesis. Many studies demonstrate that flavonoids are responsible for chemoprevention, although mechanisms of action remain to be investigated. Overall, exciting data show that dietary flavonoids could be considered as a useful cancer preventive approach. This review summarizes recent advancements on potential cancer preventive effects and mechanic insight of dietary flavonoids.
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