Dimethoxycurcumin

Dimethoxycurcumin (DiMC) is a curcuminoid compound found in Curcuma longa. Dimethoxycurcumin is also an orally active thioredoxin reductase inhibitor (IC₅₀ = 5.4 μM) and androgen receptor antagonist. Dimethoxycurcumin inhibits thioredoxin reductase, leading to oxidized thioredoxin accumulation, ROS production, DNA damage, glutathione depletion, mitochondrial membrane potential decrease, ATP depletion, S phase arrest, and apoptosis. Dimethoxycurcumin inhibits NF-κB, NADPH oxidase subunits, ATP synthase subunits, CDK4, cyclin-D1, FASN, ACC, and the IRS2-PI3K-Akt pathway, while activating AMPK, ERK, and JNK. Dimethoxycurcumin can be used for research on cancer, arsenic-induced hepatotoxicity, and tuberculosis^{[1][2][3][4][5][6][7][8][9][10][11][12]}. In Vitro:Dimethoxycurcumin (DIMC) (5-15 μM) inhibits RAW264.7 cell proliferation and induces apoptosis^[1].
Dimethoxycurcumin (5-50 μM; 8 h) simultaneously induces apoptosis and necrosis in MCF7 cells at 5 μM, whereas it primarily induces secondary apoptosis or necrosis at 25 and 50 μM^[2].
Dimethoxycurcumin (2.5 μM; 2 h) in combination with 4 Gy or 8 Gy radiation synergistically enhances radiation-induced apoptosis and mitotic catastrophe in A549 cells^[6].
Dimethoxycurcumin (5 μM; 48 h) induces a large apoptotic cell population (approximately 65%) in HCT116 cells after 48 h^[10].
Dimethoxycurcumin (10-50 μM; 3 h) is genotoxic to 786-O cells and induces DNA damage at concentrations of 10 μM and above^[11].
Dimethoxycurcumin (10-50 μM; 24 h) induces monopolar spindle formation and apoptosis in 786-O cells at concentrations of 10 μM and above^[11].
Dimethoxycurcumin (10-50 μM; 24 h) induces apoptosis in 786-O cells, with a significant increase in annexin-V-positive cells at 10 μM^[11].
Dimethoxycurcumin (24 h) activates caspase 3/7 and caspase 9 in 786-O cells^[11].
Dimethoxycurcumin (12 h) regulates the expression of genes involved in DNA repair, apoptosis, proliferation, and xenobiotic metabolism in 786-O cells^[11].
Dimethoxycurcumin (DIMC) (5-50 μM; 24 h) induces selective cytotoxicity in MCF7 cells, with weaker effects on mouse splenic lymphocytes^[2].
Dimethoxycurcumin (50 μM) combined with NAC (Acetylcysteine) (HY-B0215) (0.25-0.75 mM) inhibits Dimc-induced cytotoxicity in MCF7 cells in a concentration-dependent manner^[2].
Dimethoxycurcumin (5-50 μM; 2 h) induces dose-dependent DNA damage in MCF7 cells, manifested as an increase in tail moment in the comet assay^[2].
Dimethoxycurcumin (25-50 μM; 2-6 h) induces a significant decrease in the GSH/GSSG ratio at 2 h in MCF7 cells, followed by recovery at 6 h^[2].
Dimethoxycurcumin (25-50 μM; 2-6 h) causes a sustained decrease in ATP levels in MCF7 cells, whereas at 5 μM it induces a transient decrease followed by recovery^[2].
Dimethoxycurcumin (5-50 μM; 6 h) exhibits differential modulation of ATP synthase subunit gene expression in MCF7 cells, with 50 μM causing significant inhibition of all four subunits^[2].
Dimethoxycurcumin (DIMC) (2.5-5 μM; 2 h) sensitizes A549, PC-3, and MCF-7 cancer cells to radiation-induced loss of clonogenic capacity, with the maximum effect observed at 2.5 μM DIMC and 4 Gy radiation, resulting in a surviving fraction of 0.03^[6].
Dimethoxycurcumin (2.5 μM; 48 h) combined with 4 Gy radiation effectively eliminates cancer stem cells in A549 cells, reducing their abundance to 0.50%^[6].
Treatment with Dimethoxycurcumin (2.5 μM; 15-180 min) followed by 4 Gy radiation significantly delays DNA repair in A549 cells, as evidenced by persistent γ-H2AX and 53BP1 foci at 180 min^[6].
Dimethoxycurcumin (DMC) (5-30 μM; 24 h) exhibits potent anticancer effects against T-47D, MCF-7, MDA-MB 435S, and MDA-MB 231 breast cancer cells, with IC₅₀ values of 21.75, 23.62, 20.05, and 22.44 μM, respectively^[8].
Dimethoxycurcumin (10-30 μM; 12 h) effectively inhibits the long-term survival and clonogenic capacity of MDA-MB 435S cells at a concentration of 10 μM^[8].
Dimethoxycurcumin (20 μM; 12 h) induces pronounced cellular vacuolization in MDA-MB 435S, MDA-MB 231, MCF-7, and T-47D breast cancer cells^[8].
Dimethoxycurcumin (20 μM; 4-24 h) upregulates LC3-I and LC3-II protein levels in MDA-MB 435S and MDA-MB 231 cells, but does not affect ATG5 and ATG6 levels^[8].
Dimethoxycurcumin (5-20 μM; 16 h) induces cell vacuolation in MDA-MB 435S cells at concentrations of 5, 10, and 20 μM^[8].
Dimethoxycurcumin (20 μM; 0-24 h) downregulates Alix and activates the ERK and JNK pathways in MDA-MB 435S cells^[8].
Dimethoxycurcumin (20 μM; 0-24 h) progressively increases the accumulation of ubiquitinated proteins in MDA-MB 435S cells^[8].
Dimethoxycurcumin (10-30 μM; 6-24 h) inhibits cellular proteasome activity (chymotrypsin-like, trypsin-like, and PGPH-like) in MDA-MB 435S cells^[8].
Dimethoxycurcumin (10-30 μM; 4-24 h) upregulates CHOP, ATF4, Noxa, and Bim protein levels in MDA-MB 435S cells^[8].
Dimethoxycurcumin (compound 3) (1 nM-50 μM; 72 h) inhibits the viability of HPAF-II, BxPC-3, and CFPAC-1 pancreatic cancer cell lines with IC₅₀ values in the low micromolar range^[9].
Dimethoxycurcumin (10 µM) exhibits potent inhibitory effects on the viability of HPAF-II and BxPC-3 cells^[9].
Dimethoxycurcumin (10 µM; 12 days) completely inhibits the clonogenic ability of BxPC-3 pancreatic cancer cells^[9].
Dimethoxycurcumin (0.01-100 μM; 48 h) effectively inhibits the proliferation of HCT116 human colon cancer cells and induces cytotoxicity, with a GI₅₀ of 3.3 μM and an LC₅₀ of 38.2 μM after 48 h^[10].
Dimethoxycurcumin (5-50 μM; 48 h) significantly reduces the adherent density of HCT116 cells after 48 h, with no adherent cells remaining at 30 μM^[10].
Dimethoxycurcumin (DiMC) (2.5-50 μM; 24 h) is cytotoxic to 786-O cells with an IC₅₀ of 16 μM^[11].
Dimethoxycurcumin (2.5-50 μM; 48 h) inhibits 786-O cell proliferation in a dose-dependent manner, with a significant effect observed at 10 μM^[11].
Dimethoxycurcumin (5-50 μM; 2 h) exerts a biphasic effect on ROS generation and specifically increases superoxide anion radical production in MCF7 cells^[2].
Dimethoxycurcumin (10-50 nmoles/mL) shows concentration-dependent cellular uptake in MCF7 cells and is inhibited by exogenous GSH, which simultaneously reduces ROS generation^[2].
Dimethoxycurcumin (DIMC) (2.5 µM) increases ROS levels and slows DNA repair by inhibiting thioredoxin reductase, thereby exerting a radiosensitizing effect on A549 cells^[5].
Dimethoxycurcumin (2.5 μM; 24 h) inhibits thioredoxin reductase in a cell-free system with an IC₅₀ of 5.4 μM, and when combined with 4 Gy radiation, it significantly inhibits TrxR activity in A549 cells, whereas thioredoxin overexpression abolishes this radiosensitizing effect^[6].
Dimethoxycurcumin (5-50 μM; 6 h) induces a concentration-dependent decrease in mitochondrial membrane potential in MCF7 cells^[2].
Dimethoxycurcumin (20 μM; 8-24 h) induces progressive dilation of mitochondria and the ER in MDA-MB 435S cells, with the average width of ER-derived vacuoles reaching 4.93 μm at 24 h^[8].
Dimethoxycurcumin (20 μM; 12-24 h) induces severe ultrastructural changes in MDA-MB 435S cells, including mitochondrial swelling, megamitochondria formation, and extensive endoplasmic reticulum dilation^[8].
Dimethoxycurcumin (5-50 μM; 16 h) induces S phase cell cycle arrest and cell death in MCF7 cells^[2].
Dimethoxycurcumin (5-50 μM; 16 h) modulates the expression of cell cycle regulatory proteins (p53, p21, CDK4, cyclin-D1) and apoptotic markers (Bax, Bcl-2, Cyt c) in MCF7 cells, promoting apoptosis^[2].
Dimethoxycurcumin (DIMC) (10 mM GSH; 1 h) directly interacts with GSH in vitro^[4].
Dimethoxycurcumin (1 h) reduces basal reactive oxygen species levels in lymphocytes^[4].
Dimethoxycurcumin (4 h) depletes GSH levels in lymphocytes^[4].
Dimethoxycurcumin (1-10 μM; 4 h) inhibits PHA-induced IL-2 secretion in Jurkat cells^[4].
Dimethoxycurcumin (2.5-10 μM; 15 min-48 h) combined with 4 Gy radiation significantly increases cytosolic and mitochondrial ROS and decreases the GSH/GSSG ratio in A549 cells at 48 h^[6]. In Vivo:DiMC pre-administration (20-80 mg/kg BW/day; p.o.; daily; 4 weeks) significantly attenuates arsenic-induced oxidative hepatic injury, inflammation, and apoptosis in rats via suppression of NADPH oxidase and activation of Nrf2-Keap1 signaling^[1].
DMC (25-50 mg/kg; i.p.; every 2 days; 25 days) demonstrates more potent in vivo anticancer effects than curcumin, with 25 mg/kg DMC exceeding the tumor-reducing effect of 50 mg/kg curcumin, and this is associated with enhanced proteasome inhibition and CHOP upregulation in tumors^[8].