| Features: Estrogen-like activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genistein is a naturally occurring isoflavone predominantly found in soy products. It binds estrogen receptors (with relative preference for ERβ over ERα), inhibits certain tyrosine kinases, and modulates PI3K/AKT, NF-κB, MAPK, and cell-cycle pathways in preclinical cancer models. It is also reported to influence angiogenesis and epigenetic regulation. Oral exposure produces conjugated metabolites (glucuronides/sulfates), and free genistein plasma levels are typically much lower than many in-vitro µM concentrations. -soy isoflavone Anticancer effects through several mechanisms: -Modulation of Hormone Activity: can bind to estrogen receptors(hormone-dependent cancers like breast and prostate cancer). -Inhibition of Cell Proliferation:- -inducing cell cycle arrest. -Induction of Apoptosis:- by influencing pro- and anti-apoptotic regulators. -Anti-inflammatory and Antioxidant Effects:-antioxidant properties help to neutralize ROS -Anti-angiogenic Activity:may also inhibit tumor angiogenesis Key Cellular Signaling Pathways Involved -Estrogen Receptor Signaling: interacting with estrogen receptors (ERα and ERβ) -PI3K/Akt/mTOR Pathway:inhibits this pro-survival pathway, leading to reduced cell growth -MAPK/ERK Pathway: can contribute to cell cycle arrest. -NF-κB Pathway:may downregulate NF-κB, supporting a reduction in tumor-promoting inflammation. -Wnt/β-catenin Pathway: involved in cell proliferation, differentiation, and oncogenic transformation. Dosages often ranging from approximately 40 mg to 100 mg per day for potential therapeutic effects. Genistein has limited bioavailability when ingested as part of the diet. Efforts to enhance its absorption include the use of specific formulations, such as those that combine genistein with other compounds or utilize novel delivery systems. Genistein — a naturally occurring polyphenolic isoflavone and phytoestrogen found predominantly in soybeans and soy-derived foods, usually present in plants as glycosides that are hydrolyzed to the biologically active aglycone. It is formally classified as a dietary isoflavone, selective estrogen-receptor modulator-like phytochemical, and experimental anticancer agent. Standard abbreviations include GEN and G. Genistein preferentially engages estrogen receptor beta at lower concentrations, but can also activate estrogen receptor alpha as exposure increases; therefore, its biological effects are strongly dependent on dose, tissue, receptor expression, hormonal environment, and life stage. It is also widely used experimentally as a protein-tyrosine-kinase inhibitor, although many laboratory kinase effects require concentrations exceeding typical free systemic exposure after oral intake. Primary mechanisms (ranked):
Bioavailability / PK relevance: Oral genistein undergoes extensive intestinal and hepatic glucuronidation and sulfation. Circulating total genistein may reach micromolar concentrations after concentrated preparations, but most is conjugated; pharmacologically active free aglycone concentrations are generally substantially lower. Absorption varies with food matrix, glycoside hydrolysis, intestinal microbiota, dose, formulation, and enterohepatic recycling. Nanoparticle, lipid, phospholipid, and other delivery systems can increase experimental exposure but are not established oncology treatments. In-vitro vs systemic exposure relevance: Many anticancer studies use approximately 10–100 µM genistein, with pronounced apoptosis, topoisomerase inhibition, or G2/M arrest often occurring at 25–100 µM. These concentrations commonly exceed sustained free-genistein exposure achievable through soy foods or conventional oral supplementation. Lower nanomolar-to-low-micromolar concentrations may still modulate estrogen receptors and transcription, meaning hormonal activity may occur at exposures below those required for direct cytotoxicity. Clinical evidence status: Extensive preclinical evidence; several small phase I–II or presurgical randomized human studies, principally in prostate and bladder cancer, have evaluated tissue biomarkers and short-term safety. Some studies reported modulation of PSA-related, inflammatory, epigenetic, proliferation, or kinase biomarkers, but consistent tumor regression, recurrence reduction, progression-free survival, or overall-survival benefit has not been demonstrated. Genistein is not an established or approved anticancer therapy and should be classified as an investigational preventive or adjunctive agent rather than a cancer treatment. Particular caution is warranted in estrogen-sensitive disease, during endocrine therapy, with concentrated supplements, and where thyroid function or medication absorption is clinically important. Genistein Mechanistic Profile
P: 0–30 min R: 30 min–3 hr G: >3 hr |
| Source: CGL-Driver Genes |
| Type: Oncogene |
| A gene that encodes a cytosolic adapter protein necessary for both innate and adaptive immune response. The expression of MyD88 is elevated in tumor tissues compared to normal tissues, such as those found in breast, lung, liver, colon, and stomach organs. Researchers have drawn contradictory conclusions regarding the role of MyD88 therein. The reason may be, on one hand, inhibiting MyD88 may weaken immune function, resulting in compromised immune surveillance against tumor cells and a reduced ability to eliminate pathogenic factors. This scenario can promote the emergence and progression of tumors. On the other hand, suppressing MyD88 might alleviate inflammation, thus preventing inflammation-associated tumorigenesis. MYD88 (myeloid differentiation primary response 88) is a key adaptor protein involved in the signaling pathways of the immune system, particularly in the Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) pathways. Elevated MYD88 expression or the presence of MYD88 mutations can be associated with poor prognosis in certain cancers. |
| 7102- | GEN, | Genistein: An Integrative Overview of Its Mode of Action, Pharmacological Properties, and Health Benefits |
| - | Review, | Var, | NA |
Query results interpretion may depend on "conditions" listed in the research papers. Such Conditions may include : -low or high Dose -format for product, such as nano of lipid formations -different cell line effects -synergies with other products -if effect was for normal or cancerous cells
Filter Conditions: Pro/AntiFlg:% IllCat:% CanType:% Cells:% prod#:85 Target#:564 State#:% Dir#:2
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