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| Apigenin — a plant-derived flavone (4′,5,7-trihydroxyflavone) abundant in parsley/celery/chamomile and other dietary sources, often abbreviated APG (or “Api” in some indexes). It is a small-molecule polyphenol classified as a dietary phytochemical/nutraceutical candidate with broad pleiotropic signaling effects in oncology models (cell-cycle control, apoptosis, inflammatory signaling, metabolic stress, and invasion/angiogenesis programs), but with important translation constraints driven by low aqueous solubility and extensive phase-II conjugation. Primary mechanisms (ranked):
Bioavailability / PK relevance: Oral apigenin exposure is commonly limited by poor water solubility and extensive first-pass metabolism (glucuronidation/sulfation). Human data indicate circulating apigenin is largely present as conjugated metabolites, and dietary intake can yield only low (typically sub-µM) systemic levels; lipidic/self-emulsifying formulations can increase exposure in vivo (formulation-dependent). Reported half-life/kinetic parameters vary widely across studies and matrices. In-vitro vs systemic exposure relevance: Many anti-cancer in vitro studies use ~10–50+ µM apigenin, which can exceed typical achievable free aglycone systemic levels after oral intake; some effects may therefore be high-concentration or formulation-enabled rather than diet-achievable. Tissue-local exposure (GI lumen, local mucosa) may be higher than plasma, and conjugate biology may contribute (context-dependent). Clinical evidence status: Predominantly preclinical oncology evidence (cell and animal models) with limited, non-definitive human cancer interventional data; at least one pilot clinical study concept exists/has been registered (status-dependent). Strongest human evidence base is for non-cancer indications and general bioactivity rather than oncology efficacy. Apigenin present in parsley, celery, chamomile, oranges and beverages such as tea, beer and wine."It exhibits cell growth arrest and apoptosis in different types of tumors such as breast, lung, liver, skin, blood, colon, prostate, pancreatic, cervical, oral, and stomach, by modulating several signaling pathways." -Note half-life reports vary 2.5-90hrs?. -low solubility of apigenin in water : BioAv (improves when mixed with oil/dietary fat or lipid based formulations) -best oil might be MCT oils (medium-chain fatty acids) Pathways: - Often considered an antioxidant, in cancer cells it can paradoxically induce ROS production (one report that goes against most others, by lowering ROS in cancer cells but still effective) - ROS↑ related: MMP↓(ΔΨm), ER Stress↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, UPR↑, cl-PARP↑, HSP↓ - Lowers AntiOxidant defense in Cancer Cells: NRF2↓, GSH↓ (Conflicting evidence about Nrf2) - Combined with Metformin (reduces Nrf2) amplifies ROS production in cancer cells while sparing normal cells. - Raises AntiOxidant defense in Normal Cells: NRF2↑, SOD↑, GSH↑, Catalase↑, - lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : IL-1β↓, TNF-α↓, IL-6↓, IL-8↓ - inhibit Growth/Metastases : , MMPs↓, MMP2↓, MMP9↓, IGF-1↓, uPA↓, VEGF↓, ERK↓ - reactivate genes thereby inhibiting cancer cell growth : HDAC↓, DNMT1↓, DNMT3A↓, EZH2↓, P53↑, HSP↓ - cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓, - inhibits Migration/Invasion : TumCMig↓, TumCI↓, FAK↓, ERK↓, - inhibits glycolysis and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, PDK1↓, GLUT1↓, LDHA↓, HK2↓, Glucose↓, GlucoseCon↓ - inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, PDGF↓, EGFR↓, Integrins↓, - inhibits Cancer Stem Cells : CSC↓, CK2↓, Hh↓, GLi↓, GLi1↓, - Others: PI3K↓, AKT↓, JAK↓, 1, 2, 3, STAT↓, 1, 2, 3, 4, 5, 6, Wnt↓, β-catenin↓, AMPK↓,, α↓,, ERK↓, 5↓, JNK↓, - Shown to modulate the nuclear translocation of SREBP-2 (related to cholesterol). - Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes) -Ex: other flavonoids(chrysin, Luteolin, querectin) curcumin, metformin, sulforaphane, ASA Neuroprotective, Renoprotection, Hepatoprotective, CardioProtective, - Selectivity: Cancer Cells vs Normal Cells Apigenin exhibits biological effects (anticancer, anti-inflammatory, antioxidant, neuroprotective, etc.) typically at concentrations roughly in the range of 1–50 µM. Parsley microgreens can contain up to 2-3 times more apigenin than mature parsley. Apigenin is typically measured in the range of 1-10 μM for biological activity. Assuming a molecular weight of 270 g/mol for apigenin, we can estimate the following μM concentrations: 10uM*5L(blood)*270g/mol=13.5mg apigenin (assumes 100% bioavailability) then an estimated 10-20 mg of apigenin per 100 g of fresh weight parlsey 2.2mg/g of apigenin fresh parsley 45mg/g of apigenin in dried parsley (wikipedia) so 100g of parsley might acheive 10uM blood serum level (100% bioavailability) BUT bioavailability is only 1-5% (Supplements available in 75mg liposomal)( Apigenin Pro Liposomal, 200 mg from mcsformulas.com) A study had 2g/kg bw (meaning 160g for 80kg person) delivered a maximum 0.13uM of plasma concentration @ 7.2hrs. Assuming parsley is 90-95% water, then that would be ~16g of dried parsley Conclusion: to reach 10uM would seem very difficult by oral ingestion of parsley. Other quotes: “4g of dried parsley will be enough for 50kg adult” 5mg/kg BW yields 16uM, so 80Kg person means 400mg (if dried parsley is 130mg/g, then would need 3g/d) In many cancer cell lines, concentrations in the range of approximately 20–40 µM have been reported to shift apigenin’s activity from mild antioxidant effects (or negligible ROS changes) toward a clear pro-oxidant effect with measurable ROS increases. Low doses: At lower concentrations, apigenin is more likely to exhibit its antioxidant properties, scavenging ROS and protecting cells from oxidative stress. In normal cells with robust antioxidant systems, apigenin’s antioxidant effects might prevail, whereas cancer cells—often characterized by an already high level of basal ROS—can be pushed over the oxidative threshold by increased ROS production induced by apigenin. In environments with lower free copper levels, this pro-oxidant activity is less pronounced, and apigenin may tilt the balance toward its antioxidant function. Apigenin — cancer-relevant mechanistic pathway matrix
TSF P: 0–30 min |
| Source: HalifaxProj(attenuate) TCGA |
| Type: |
| Cyclins and cyclin-dependent kinases (CDKs) are key regulators of the cell cycle, and their dysregulation is a common feature in many cancers. The cell cycle consists of several phases: G1 Phase (Gap 1): The cell grows and prepares for DNA synthesis. S Phase (Synthesis): DNA is replicated. G2 Phase (Gap 2): The cell prepares for mitosis. M Phase (Mitosis): The cell divides into two daughter cells. Open menu Cdh1 and E-cadherin are they the same thing Cdh1 and E-cadherin refer to the same protein. Cdh1 is the gene that encodes E-cadherin, which is a type of cadherin, a family of proteins involved in cell-cell adhesion. E-cadherin plays a crucial role in maintaining the structure and integrity of tissues by facilitating adhesion between epithelial cells. It is particularly important in the context of development and in the maintenance of epithelial tissue architecture. In summary, Cdh1 is the gene name, while E-cadherin is the protein product of that gene. CDK1/2/5/9 role in cancer Cyclin-dependent kinases (CDKs) are a family of protein kinases that play essential roles in regulating the cell cycle, transcription, and other cellular processes. CDK1, CDK2, CDK5, and CDK9 have been implicated in cancer through various mechanisms: CDK1: Role: Primarily involved in the regulation of the cell cycle, particularly the transition from G2 phase to mitosis. Cancer Implication: Overexpression or hyperactivation of CDK1 can lead to uncontrolled cell proliferation and is often associated with various cancers, including breast, colorectal, and lung cancers. CDK1 inhibitors are being explored as potential cancer therapies. CDK2: Role: Functions mainly in the G1 to S phase transition of the cell cycle, working closely with cyclins D and E. Cancer Implication: CDK2 is often overexpressed in cancer cells, contributing to tumorigenesis by promoting cell cycle progression. Inhibition of CDK2 has been studied as a therapeutic strategy in cancers such as ovarian and breast cancer. CDK5: Role: Unlike other CDKs, CDK5 is primarily involved in neuronal function and is activated by p35 and p39. It plays roles in neuronal development and synaptic function. Cancer Implication: CDK5 has been implicated in certain cancers, particularly in the context of neurodegenerative diseases and brain tumors. Its role in cancer is complex, as it can promote or inhibit tumor growth depending on the context and the specific cancer type. CDK9: Role: Part of the positive transcription elongation factor b (P-TEFb) complex, CDK9 is involved in regulating transcription by phosphorylating the C-terminal domain of RNA polymerase II. Cancer Implication: CDK9 is often overexpressed in various cancers, leading to increased transcription of genes that promote cell survival and proliferation. Inhibitors of CDK9 are being investigated as potential cancer therapies, particularly in hematological malignancies. In summary, CDK1, CDK2, CDK5, and CDK9 each play distinct roles in cell cycle regulation and transcription, and their dysregulation is associated with various cancer types. Targeting these kinases with specific inhibitors is an area of active research in cancer therapy. CDK4 and CDK6 are cyclin-dependent kinases that play crucial roles in regulating the cell cycle, particularly the transition from the G1 phase to the S phase. Their activity is tightly regulated by cyclins, specifically cyclin D, and they are essential for cell proliferation. Here’s how CDK4 and CDK6 are implicated in cancer: Role in Cell Cycle Regulation CDK4/6 Function: CDK4 and CDK6, when activated by cyclin D, phosphorylate the retinoblastoma protein (Rb). This phosphorylation leads to the release of E2F transcription factors, which promote the expression of genes necessary for DNA synthesis and progression into the S phase of the cell cycle. Implications in Cancer Overexpression and Dysregulation: In many cancers, CDK4 and CDK6 are often overexpressed or hyperactivated, leading to uncontrolled cell proliferation. This dysregulation can result from various factors, including mutations in cyclins, loss of tumor suppressor genes (like Rb), or amplification of the CDK4/6 genes themselves. Breast Cancer: CDK4/6 is particularly well-studied in hormone receptor-positive breast cancer. In these cancers, the overactivity of CDK4/6 contributes to tumor growth and progression. Other Cancers: CDK4/6 has also been implicated in other cancers, including melanoma, lung cancer, and certain hematological malignancies. Therapeutic Targeting CDK4/6 Inhibitors: The discovery of the role of CDK4 and CDK6 in cancer has led to the development of specific inhibitors, such as palbociclib, ribociclib, and abemaciclib. These drugs have shown efficacy in treating hormone receptor-positive breast cancer, often in combination with endocrine therapies (like aromatase inhibitors or tamoxifen). Mechanism of Action: By inhibiting CDK4/6, these drugs prevent the phosphorylation of Rb, thereby blocking the cell cycle progression from G1 to S phase, leading to reduced cell proliferation and increased apoptosis in cancer cells. Conclusion CDK4 and CDK6 are critical regulators of the cell cycle, and their dysregulation is a common feature in various cancers. Targeting these kinases with specific inhibitors has become a promising therapeutic strategy, particularly in hormone receptor-positive breast cancer, and ongoing research continues to explore their role in other malignancies. Cell cycle (CDKs/cyclins) and cancer The cell cycle is a tightly regulated series of events that lead to cell division and replication. Cyclins and cyclin-dependent kinases (CDKs) are key regulators of the cell cycle, and their dysregulation is a common feature in many cancers. Here’s an overview of how CDKs and cyclins function in the cell cycle and their implications in cancer: Cell Cycle Phases The cell cycle consists of several phases: G1 Phase (Gap 1): The cell grows and prepares for DNA synthesis. S Phase (Synthesis): DNA is replicated. G2 Phase (Gap 2): The cell prepares for mitosis. M Phase (Mitosis): The cell divides into two daughter cells. Role of CDKs and Cyclins Cyclins: These are regulatory proteins whose levels fluctuate throughout the cell cycle. They activate CDKs by binding to them, forming cyclin-CDK complexes that drive the cell cycle forward. CDKs: These are serine/threonine kinases that, when activated by cyclins, phosphorylate target proteins to regulate various processes, including: Progression through the cell cycle. DNA replication. Mitotic entry and exit. Key CDKs and Their Functions CDK1: Regulates the transition from G2 to M phase. CDK2: Involved in the G1 to S phase transition. CDK4 and CDK6: Work with cyclin D to promote progression through the G1 phase. CDK2: Also works with cyclin E to facilitate the G1/S transition. FRO9: Involved in transcriptional regulation and elongation. Overexpression: Many cancers exhibit overexpression of cyclins (e.g., cyclin D1) or CDKs (e.g., CDK4/6), leading to uncontrolled cell proliferation. |
| 311- | Api, | Apigenin inhibits the proliferation of adenoid cystic carcinoma via suppression of glucose transporter-1 |
| - | in-vitro, | ACC, | 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
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