dna fragmentation

Z-FA-FMK can irreversibly inhibit cysteine protease and also inhibit effector caspases.

5-Geranoxy-7-methoxycoumarin shows antifungal activity.

Daniquidone (Batracylin) is a potent dual inhibitor of DNA topoisomerase I and DNA topoisomerase II with cytotoxic and antiproliferative activity that induces DNA fragmentation for the study of neoplasms, immune disorders, and lymphatic disorders.

Metaldehyde (Metacetaldehyde) is an agriculturally used molluscicide that induces DNA fragmentation in cells.

2-Methoxyestradiol (2-ME2) is an orally bioavailable estradiol metabolite with potential antineoplastic activity. 2-Methoxyestradiol inhibits angiogenesis by reducing endothelial cell proliferation and inducing endothelial cell apoptosis. This agent also inhibits tumor cell growth by binding to tubulin, resulting in antimitotic activity, and by inducing caspase activation, resulting in cell cycle arrest in the G2 phase, DNA fragmentation, and apoptosis.

Thymidine-5'-monophosphate disodium salt (TMP DISODIUM SALT) is found in DNA. In mammalian cells, thymidine deprivation induces chromosome aberrations such as chromatid breaks, chromatid interchanges, and chromosome fragmentation.

Citric acid (Citro) is a weak organic tricarboxylic acid found in citrus fruits. Citric acid is a food additive and a natural preservative.

ALPHA-PINENE ((-)-Alpha-Pinene) is a bicyclic monoterpene found in pine trees and other plants, including Cannabis with diverse biological activities [1]. It reduces the growth of a panel of seven Gram-positive bacteria, seven Gram-negative bacteria, and eight yeast strains with MIC values of 0.75-1.29, 1.05-1.59, and 0.7-1.17%, respectively [2]. It has insecticidal activity against C. molestus larvae with LC50 values ranging from 47 to 49 mg/L.3 ALPHA-PINENE (100 μg/ml) induces apoptosis, increases anion superoxide production and DNA fragmentation, and activates caspase-3 in B16/F10 melanoma cells [4]. In a B16/F10 mouse xenograft model, ALPHA-PINENE(100 ml of a 10 mg/ml solution) reduces the number of metastatic lung nodules by approximately 7-fold. ALPHA-PINENE(8.6 mg/L, aerosol) also increases the time spent in the open arms of the elevated plus maze by approximately 2-fold in mice, indicating anxiolytic-like activity [5].

1,4-Anthraquinone is an anticancer drug that blocks nucleoside transport, inhibits macromolecule synthesis, induces DNA fragmentation, and decreases the growth and viability of L1210 leukemic cells in the same nanomolar range as daunorubicin in vitro.1,4-

MDK83190 (Apoptosis Activator 2) is a potent apoptosis activator, induceing caspase-3 activation, PARP cleavage, and DNA fragmentation .

N-Nitroso Atenolol is a derivative of Atenolol. At concentrations ranging from 0.1 to 1 mM, it induces DNA fragmentation in rat hepatocytes.

Apoptosisinducer 15 (Compound 3) induces apoptosis and causes cell cycle arrest at the G2/M phase. While it exhibits cytotoxicity, it does not cause DNA fragmentation.

PeS-9 is an androgen receptor (AR) degrader that induces the degradation of androgen receptors. It enhances the production of cytotoxic reactive oxygen species (ROS), leading to mitochondrial and endoplasmic reticulum stress, which results in the release of mitochondrial cytochrome C and AIF. PeS-9 activates caspase-9 and caspase-3, causing DNA fragmentation and apoptosis. It exhibits anti-prostate cancer activity and demonstrates antitumor and antimetastatic effects in vivo with minimal side effects. PeS-9 is applicable for targeted therapy research in GLUT-1 overexpressing tumors.

TMPO (3,3,5,5-Tetramethyl-1-pyrroline 1-oxide) is a spin-trapping agent that targets free radicals. It scavenges superoxide anions and hydroxyl radicals, and inhibits thymocyte apoptosis with an EC50 value of 19.1 mM for DNA fragmentation induced by MPS and 30.7 mM by Etoposide. TMPO reacts with intracellular free radicals to form stable nitroxide radical products, thereby reducing oxidative stress (such as lowering peroxide levels and maintaining glutathione content) and blocking oxidative events in the apoptosis pathway. TMPO shows potential for research in apoptosis of immune cells like thymocytes.

[1,3-Bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene](chloro)silver is a silver-N-heterocyclic carbene (Silver-NHC) complex with potent anticancer activity. It effectively inhibits the proliferation of various cancer cell lines by inducing apoptosis. Distinct from classical pathways, its mechanism is independent of caspase activation. Instead, it triggers the release of mitochondrial Apoptosis-Inducing Factor (AIF), which translocates to the nucleus to cause chromatin condensation and large-scale DNA fragmentation. As a novel organometallic anticancer lead, SIPrAgCl holds significant promise for research aimed at overcoming conventional drug resistance in tumors.

GRI977143 is a selective and non-lipid agonist of LPA2 (EC50 = 3.3 μM). GRI977143 inhibits the activation of caspases 3, 7, 8, and 9 and and reduces DNA fragmentation.

NC182 is a topo II inhibitor that shows selective and potent topo II inhibition on the induction of topo II-dependent DNA fragmentation.

4-oxo-27-TBDMS Withaferin A is a derivative of the steroidal lactone withaferin A that has anticancer activity.1 It is cytotoxic to A2780 ovarian cancer cells (IC50 = 17 μM) but not to carboplatin-resistant A2780 (A2780/CP70) cells (IC50 = >100 μM). It is selective for A2780 cells over non-cancerous ARPE19 cells (IC50 = 1,660 μM). 4-oxo-27-TBDMS Withaferin A induces DNA fragmentation in A2780 cells.References1. Perestelo, N.R., Llanos, G.G., Reyes, C.P., et al. Expanding the chemical space of withaferin A by incorporating silicon to improve its clinical potential on human ovarian carcinoma cells. J. Med. Chem. 62(9), 4571-4585 (2019). 4-oxo-27-TBDMS Withaferin A is a derivative of the steroidal lactone withaferin A that has anticancer activity.1 It is cytotoxic to A2780 ovarian cancer cells (IC50 = 17 μM) but not to carboplatin-resistant A2780 (A2780/CP70) cells (IC50 = >100 μM). It is selective for A2780 cells over non-cancerous ARPE19 cells (IC50 = 1,660 μM). 4-oxo-27-TBDMS Withaferin A induces DNA fragmentation in A2780 cells. References1. Perestelo, N.R., Llanos, G.G., Reyes, C.P., et al. Expanding the chemical space of withaferin A by incorporating silicon to improve its clinical potential on human ovarian carcinoma cells. J. Med. Chem. 62(9), 4571-4585 (2019).

C8 D-threo Ceramide is a bioactive sphingolipid and cell-permeable analog of naturally occurring ceramides. It is cytotoxic to U937 cells (IC50 = 17 μM) and induces nuclear DNA fragmentation 5- to 6-fold more potently than C8 ceramide . C8 D-threo Ceramide is a substrate for E. coli diacylglycerol kinase. It activates ceramide-activated protein kinase (CAPK) in U937 cells. C8 D-threo Ceramide also enhances V. cholerae cytolysin pore formation in liposome lipid membranes, as measured by calcein release, with a 50% release dose (RD50) value of ~5 μg/ml.

C8 L-threo Ceramide is a bioactive sphingolipid and cell-permeable analog of naturally occurring ceramides. It is cytotoxic to U937 cells (IC50 = 10 μM) and, like C8 D-threo ceramide , induces nuclear DNA fragmentation 5- to 6-fold more potently than C8 L-erythro ceramide . C8 D-threo Ceramide also enhances V. cholerae cytolysin pore formation in liposome lipid membranes, as measured by calcein release, with a 50% release dose (RD50) value of ~30 μg/ml.

9(E),11(E),13(E)-Octadecatrienoic acid (β-ESA) is a conjugated polyunsaturated fatty acid that is found in plant seed oils and in mixtures of conjugated linolenic acids synthesized by the alkaline isomerization of linolenic acid. It reduces growth of Caco-2 colon cancer cells in a dose-dependent and time-dependent manner. In vitro, β-ESA induces DNA fragmentation and upregulation of pro-apoptotic Bax mRNA. β-ESA decreases protein expression of the apoptosis suppression factor Bcl-2 and induces apoptosis in T24 bladder cancer cells via production of reactive oxygen species. It also inhibits bacterial fatty acid dioxygenase with a Ki value of 49 nM in vitro.

C2 Phytoceramide is a bioactive semisynthetic sphingolipid that inhibits formyl peptide-induced oxidant release (IC50 = 0.38 μM) in suspended polymorphonuclear cells. It increases COX-2 protein levels 15-fold through ERK signaling. It induces death of keratinocytes (20% viability) with an ED50 value of 30 μM, the same concentration at which 35% of cells in a TUNEL assay are apoptotic. C2 Phytoceramide also has antiproliferative effects in CHO cells, with greater than 80% cytotoxicity achieved at a concentration of 20 μM, and induces internucleosomal DNA fragmentation. In addition, it inhibits the activation of phospholipase D (PLD) mediated by muscarinic acetylcholine receptors in vitro.

Nemorosone is a polycyclic polyprenylated acylphloroglucinol (PPAP) originally isolated from C. rosea that has antiproliferative properties.1 Nemorosone inhibits growth of NB69, Kelly, SK-N-AS, and LAN-1 neuroblastoma cells (IC50s = 3.1-6.3 μM), including several drug-resistant clones, but not MRC-5 human embryonic fibroblasts (IC50 = >40 μM).2 It increases DNA fragmentation in LAN-1 cells in a dose-dependent manner, and decreases N-Myc protein levels and phosphorylation of ERK1/2 by MEK1/2. Nemorosone also inhibits growth of Capan-1, AsPC-1, and MIA-PaCa-2 pancreatic cancer cells (IC50s = 4.5-5.0 μM following a 72-hour treatment) but not human dermal and foreskin fibroblasts (IC50s = >35 μM).1 It induces apoptosis, abolishes the mitochondrial membrane potential, and increases cytosolic calcium concentration in pancreatic cancer cells in a dose-dependent manner. Nemorosone activates the caspase cascade in a dose-dependent manner and inhibits cell cycle progression, increasing the proportion of cells in the G0/G1 phase, in both neuroblastoma and pancreatic cancer cells.1,2 Nemorosone (50 mg/kg, i.p., per day) also reduces tumor growth in an MIA-PaCa-2 mouse xenograft model.3References1. Holtrup, F., Bauer, A., Fellenberg, K., et al. Microarray analysis of nemorosone-induced cytotoxic effects on pancreatic cancer cells reveals activation of the unfolded protein response (UPR). Br. J. Pharmacol. 162(5), 1045-1059 (2011).2. Díaz-Carballo, D., Malak, S., Bardenheuer, W., et al. Cytotoxic activity of nemorosone in neuroblastoma cells. J. Cell. Mol. Med. 12(6B), 2598-2608 (2008).3. Wold, R.J., Hilger, R.A., Hoheisel, J.D., et al. In vivo activity and pharmacokinetics of nemorosone on pancreatic cancer xenografts. PLoS One 8(9), e74555 (2013). Nemorosone is a polycyclic polyprenylated acylphloroglucinol (PPAP) originally isolated from C. rosea that has antiproliferative properties.1 Nemorosone inhibits growth of NB69, Kelly, SK-N-AS, and LAN-1 neuroblastoma cells (IC50s = 3.1-6.3 μM), including several drug-resistant clones, but not MRC-5 human embryonic fibroblasts (IC50 = >40 μM).2 It increases DNA fragmentation in LAN-1 cells in a dose-dependent manner, and decreases N-Myc protein levels and phosphorylation of ERK1/2 by MEK1/2. Nemorosone also inhibits growth of Capan-1, AsPC-1, and MIA-PaCa-2 pancreatic cancer cells (IC50s = 4.5-5.0 μM following a 72-hour treatment) but not human dermal and foreskin fibroblasts (IC50s = >35 μM).1 It induces apoptosis, abolishes the mitochondrial membrane potential, and increases cytosolic calcium concentration in pancreatic cancer cells in a dose-dependent manner. Nemorosone activates the caspase cascade in a dose-dependent manner and inhibits cell cycle progression, increasing the proportion of cells in the G0/G1 phase, in both neuroblastoma and pancreatic cancer cells.1,2 Nemorosone (50 mg/kg, i.p., per day) also reduces tumor growth in an MIA-PaCa-2 mouse xenograft model.3 References1. Holtrup, F., Bauer, A., Fellenberg, K., et al. Microarray analysis of nemorosone-induced cytotoxic effects on pancreatic cancer cells reveals activation of the unfolded protein response (UPR). Br. J. Pharmacol. 162(5), 1045-1059 (2011).2. Díaz-Carballo, D., Malak, S., Bardenheuer, W., et al. Cytotoxic activity of nemorosone in neuroblastoma cells. J. Cell. Mol. Med. 12(6B), 2598-2608 (2008).3. Wold, R.J., Hilger, R.A., Hoheisel, J.D., et al. In vivo activity and pharmacokinetics of nemorosone on pancreatic cancer xenografts. PLoS One 8(9), e74555 (2013).

MMP-2/9-IN-1 (Compound 4a) is a potent dual inhibitor of MMP-2 (IC50: 56 nM) and MMP-9 (IC50: 38 nM), leading to DNA fragmentation.