| Features: | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Caffeic acid is a polyphenol antioxidant found in coffee, fruits, vegetables, and herbs. It may have anti-inflammatory, anticancer, anti-aging, and other health benefits. Caffeic acid (CA) is a dietary hydroxycinnamic acid found widely in plant foods and in coffee largely as chlorogenic acids (caffeoylquinic acids). CA is generally antioxidant / anti-inflammatory and is frequently reported to modulate Nrf2 and NF-κB signaling, with downstream effects on survival pathways (PI3K/AKT), MAPKs, cell cycle, and apoptosis in preclinical cancer models. A notable mechanistic nuance is a context-dependent pro-oxidant effect described in the presence of copper (Cu), where CA can drive oxidative DNA damage in vitro (often discussed as potentially relevant to tumors with higher copper levels). -Caffeic acid phenethyl ester, the main representative component of propolis -Black chokeberry 141.14 mg/100 g F -Sunflower seed, meal 8.17 mg/100 g FW -Common sage, dried 26.40 mg/100 g FW -Ceylan cinnamon 24.20 mg/100 g FW -Nutmeg 16.30 mg/100 g FW -Dual capacity of CA to act as an antioxidant during carcinogenesis and as a pro-oxidant against cancer cells, promoting their apoptosis or sensitizing them to chemotherapeutic drugs. Pathways: -Caffeic acid is a potent antioxidant -Caffeic acid may also exhibit pro-oxidant behavior. At higher concentrations( 50–100 µM ?) or/and in the presence of transition metal ions (such as copper or iron), caffeic acid can participate in Fenton-like reactions, potentially leading to increased ROS generation. -Shown to inhibit NF-κB activation -Inhibitory effects on MAPK/ERK Pathway -PI3K/Akt Signaling Pathway -Activation of the Nrf2/ARE pathway -Cell cycle arrest at various checkpoints -Angiogenesis Inhibition Caffeic acid typically shows low oral bioavailability (sometimes only a few percent of the ingested dose is systemically available) and a short plasma half-life (around 1–2 hours in animal models). Caffeic acid — Caffeic acid is a dietary hydroxycinnamic acid polyphenol present in coffee, fruits, vegetables, and many herbs, and is also generated from hydrolysis of chlorogenic acids. It is formally classified as a small-molecule plant phenolic acid with redox-active, anti-inflammatory, and signal-modulating properties. Standard abbreviations include CA for caffeic acid; it should be distinguished from CAPE (caffeic acid phenethyl ester), which is a different propolis-derived ester with overlapping but not identical pharmacology. In cancer research, CA is best viewed as a pleiotropic preclinical modulator of inflammatory signaling, stress adaptation, metabolism, apoptosis, invasion, and angiogenesis, with translation limited by rapid conjugation and generally low free-aglycone systemic exposure. Primary mechanisms (ranked):
Bioavailability / PK relevance: CA is absorbable in humans, but after oral intake much of the circulating material appears rapidly as sulfate, glucuronide, and methylated metabolites rather than persistent free aglycone. Peak plasma timing is typically early, and delivery is constrained less by gut uptake than by fast metabolic conversion and short-lived free exposure. In-vitro vs systemic exposure relevance: Many anticancer studies use tens of micromolar CA, and some mechanistic claims depend on 50–100 µM or higher conditions that are not reliably reproduced as sustained free systemic exposure after ordinary oral intake. Accordingly, anti-inflammatory/adjuvant interpretations translate better than claims requiring strong direct tumor-cidal free-drug concentrations; metal-assisted pro-oxidant effects are especially context-dependent. Clinical evidence status: Primarily preclinical. The cancer evidence base consists mainly of cell and animal studies, with some adjunct/chemosensitization signals. Human oncology evidence remains very limited; at least one registered esophageal squamous cell carcinoma trial has been reported, but caffeic acid is not an established anticancer drug or standard adjunct. Mechanistic matrix
Time-Scale Flag (TSF): P / R / G
|
| Source: |
| Type: |
| In all eukaryotic cells, intracellular Ca2+ levels are maintained at low resting concentrations (approximately 100 nM) by the activity of the major Ca2+ extrusion system, the plasma membrane Ca2+-ATPase (PMCA), which exchanges extracellular protons (H+) for cytosolic Ca2+. Indeed, sustained elevation of [Ca2+]C in the form of overload, saturating all Ca2+-dependent effectors, prolonged decrease in [Ca2+]ER, causing ER stress response, and high [Ca2+]M, inducing mitochondrial permeability transition (MPT), are considered to be pro-death factors. In cancer the Ca2+-handling toolkit undergoes profound remodelling (figure 1) to favour activation of Ca2+-dependent transcription factors, such as the nuclear factor of activated T cells (NFAT), c-Myc, c-Jun, c-Fos that promote hypertrophic growth via induction of the expression of the G1 and G1/S phase transition cyclins (D and E) and associated cyclin-dependent kinases (CDK4 and CDK2). Thus, cancer cells may evade apoptosis through decreasing calcium influx into the cytoplasm. This can be achieved by either downregulation of the expression of plasma membrane Ca2+-permeable ion channels or by reducing the effectiveness of the signalling pathways that activate these channels. Such protective measures would largely diminish the possibility of Ca2+ overload in response to pro-apoptotic stimuli, thereby impairing the effectiveness of mitochondrial and cytoplasmic apoptotic pathways. Voltage-Gated Calcium Channels (VGCCs): Overexpression of VGCCs has been associated with increased tumor growth and metastasis in various cancers, including breast and prostate cancer. Store-Operated Calcium Entry (SOCE): SOCE mechanisms, such as STIM1 and ORAI1, are often upregulated in cancer cells, contributing to enhanced cell survival and proliferation. High intracellular calcium levels are associated with increased cell proliferation and migration, leading to a poorer prognosis. Calcium signaling can also influence hormone receptor status, affecting treatment responses. Increased Ca²⁺ signaling is associated with advanced disease and metastasis. Patients with higher CaSR expression may have a worse prognosis due to enhanced tumor growth and resistance to apoptosis. -Ca2+ is an important regulator of the electric charge distribution of bio-membranes. |
| 1651- | CA, | PBG, | Caffeic acid and its derivatives as potential modulators of oncogenic molecular pathways: New hope in the fight against cancer |
| - | Review, | Var, | NA |
| 1650- | CA, | Adjuvant Properties of Caffeic Acid in Cancer Treatment |
| - | 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#:51 Target#:38 State#:% Dir#:2
wNotes=0 sortOrder:rid,rpid