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| An ester formed by the condensation of gallic acid and propanol. Propyl gallate (PG), chemically known as propyl-3,4,5-trihydroxybenzoate, is widely present in processed food and cosmetics, hair products, and lubricants. PG alone demonstrated antioxidative and cytoprotective properties against cellular damage and gained a pro-oxidative property in combination with copper (II). It was reported that PG was one of the most active compounds capable of generating H2O2 in DMEM media Main cancer-relevant pathways modulated by propyl gallate A. Redox imbalance & oxidative stress (dominant) -↑ Intracellular ROS (context- and dose-dependent) -Pro-oxidant in cancer cells with high basal ROS -Mitochondrial superoxide accumulation -Thiol depletion (↓ GSH, ↓ Trx buffering capacity) Importance: ★★★★★ (Primary mechanism) B. Mitochondrial dysfunction & intrinsic apoptosis -↑ MOMP → caspase cascade -Loss of mitochondrial membrane potential (ΔΨm) -Cytochrome-c release -Caspase-9 → caspase-3 activation -↑ Bax / ↓ Bcl-2 ratio Importance: ★★★★☆ C. ER stress & unfolded protein response (UPR) -↑ PERK–eIF2α–ATF4–CHOP -ROS-linked protein misfolding -Pro-apoptotic UPR signaling dominates over adaptive UPR Importance: ★★★☆☆ D. Cell cycle disruption -G1 or G2/M arrest (cell-type dependent) -↓ Cyclin D1, Cyclin B1 -↑ p21, p27 Importance: ★★☆☆☆ E. MAPK stress signaling -↑ JNK / p38 -Stress-activated apoptosis signaling -Often precedes mitochondrial failure Importance: ★★☆☆☆ F. Inflammation & survival pathways (secondary) -↓ NF-κB, ↓ STAT3 (indirect) -Suppression is largely ROS-mediated, not direct inhibition -Reduced anti-apoptotic gene transcription Importance: ★★☆☆☆ G. NRF2–ARE signaling (dual role) -Low dose: NRF2 activation → cytoprotection -High dose / cancer cells: NRF2 overwhelmed → apoptosis Importance: ★★☆☆☆ (Highly context dependent; double-edged)
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| Source: TCGA |
| Type: Antiapoptotic |
| Nrf2 is responsible for regulating an extensive panel of antioxidant enzymes involved in the detoxification and elimination of oxidative stress. Thought of as "Master Regulator" of antioxidant response. -One way to estimate Nrf2 induction is through the expression of NQO1. NQO1, the most potent inducer: SFN 0.2 μM, quercetin (2.5 μM), curcumin (2.7 μM), Silymarin (3.6 μM), tamoxifen (5.9 μM), genistein (6.2 μM ), beta-carotene (7.2μM), lutein (17 μM), resveratrol (21 μM), indol-3-carbinol (50 μM), chlorophyll (250 μM), alpha-cryptoxanthin (1.8 mM), and zeaxanthin (2.2 mM) 1. Raising Nrf2 enhances the cell's antioxidant defenses and ↓ROS. This strategy is used to decrease chemo-radio side effects. 2. Downregulating Nrf2 lowers antioxidant defenses and ↑ROS. In cancer cells this leads to DNA damage, and cell death. 3. However there are some cases where increasing Nrf2 paradoxically causes an increase in ROS (cancer cells). Such as cases of Mitochondial overload, signal crosstalk, reductive stress -In some cases, Nrf2 is overexpressed in cancer cells, which can lead to the activation of genes involved in cell proliferation, angiogenesis, and metastasis. This can contribute to the development of resistance to chemotherapy and targeted therapies. -Increased Nrf2 expression: Lung, Breast, Colorectal, Prostrate. Decreased Nrf2 expression: Skine, Liver, Pancreatic. -Nrf2 is a cytoprotective transcription factor which demonstrated both a negative effect as well as a positive effect on cancer - "promotes Nrf2 translocation from the cytoplasm to the nucleus," means facilitates the movement of Nrf2 into the nucleus, thereby enhancing the cell's antioxidant and cytoprotective responses. -Major regulator of Nrf2 activity in cells is the cytosolic inhibitor Keap1. Nrf2 Inhibitors and Activators Nrf2 Inhibitors: Brusatol, Luteolin, Trigonelline, VitC, Retinoic acid, Chrysin Nrf2 Activators: SFN, OPZ EGCG, Resveratrol, DATS, CUR, CDDO, Api - potent Nrf2 inducers from plants include sulforaphane, curcumin, EGCG, resveratrol, caffeic acid phenethyl ester, wasabi, cafestol and kahweol (coffee), cinnamon, ginger, garlic, lycopene, rosemany Nrf2 plays dual roles in that it can protect normal tissues against oxidative damage and can act as an oncogenic protein in tumor tissue. – In healthy tissues, NRF2 activation helps protect cells from oxidative damage and maintains cellular homeostasis. – In many cancers, constitutive activation of NRF2 (often through mutations in NRF2 itself or loss-of-function mutations in KEAP1) leads to an enhanced antioxidant capacity. – This upregulation can promote tumor cell survival by enabling cancer cells to thrive under oxidative stress, resist chemotherapeutic agents, and sustain metabolic reprogramming. – Elevated NRF2 levels have been implicated in promoting tumor growth, metastasis, and resistance to therapy in various malignancies. – High or sustained NRF2 activity is frequently associated with aggressive tumor phenotypes, poorer prognosis, and decreased overall survival in several cancer types. – While its activation is essential for protecting normal cells from oxidative stress, aberrant or sustained NRF2 activation in tumor cells can lead to enhanced survival, therapeutic resistance, and tumor progression. NRF2 inhibitors: (to decrease antioxidant defenses and increase cell death from ROS). -Brusatol: most cited natural inhibitors of Nrf2. -Luteolin: luteolin can reduce Nrf2 activity in specific cancer models and may enhance cell sensitivity to chemotherapy. However, luteolin is also known as an antioxidant, and its influence on Nrf2 can sometimes be context dependent. -Apigenin: certain studies to down‑regulate Nrf2 in cancer cells: Dose and context dependent . -Oridonin: -Wogonin: although its effects might be cell‑ and dose‑specific. - Withaferin A |
| 5217- | PG, | Role of redox signaling regulation in propyl gallate-induced apoptosis of human leukemia cells |
| - | in-vitro, | AML, | THP1 | - | in-vitro, | AML, | Jurkat | - | in-vitro, | AML, | HL-60 |
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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