Artocarpin

Artocarpin is an orally active apoptosis inducer. Artocarpin targets NF-κB, Erk1/2, p38 MAPK, AktS473, p53, Akt 1 kinase and Akt 2 kinase. Artocarpin induces reactive oxygen species (ROS) production, mediates p53-dependent and p53-independent apoptotic signaling pathways, induces G1-phase cell cycle arrest, and triggers autophagic cell death. Artocarpin exerts cytotoxic and bactericidal effects on cancer cells, reduces bacterial load, and exhibits anti-inflammatory, analgesic and anti-angiogenic activities^{[1][2][3][4][5][6][7]}. In Vitro:Artocarpin (0-20 μM; 24 h) induces concentration-dependent apoptosis in A549 and H1299 NSCLC cells, as evidenced by increased DNA fragmentation, subG₁ phase cell accumulation, and early/late apoptotic cell populations after 24-hour treatment^[1].
Artocarpin (0-25 μM; 0-120 min) induces time- and concentration-dependent ROS generation in A549 and H1299 NSCLC cells via a NADPH oxidase (Nox)-dependent pathway, but does not induce ROS in normal human pulmonary epithelial cells (HPAEpiCs)^[1].
Artocarpin (10 μM; 0-24 h) induces ROS- and MAPK-dependent activation of the p53 apoptotic pathway, increasing expression of phosphorylated p53, PUMA, cytochrome c, Apaf-1, and cleaved caspase-3 in A549 NSCLC cells over 24 hours^[1].
Artocarpin (10 μM; 0-24 h) induces ROS- and Akt-dependent activation of NF-κB, leading to increased expression of c-Myc and Noxa in A549 and H1299 NSCLC cells^[1].
Artocarpin (10-20 μM; 48 h, 3-48 h) induces apoptosis and autophagy in DLD1, HCT15, and HT29 human colon adenocarcinoma cells, as evidenced by PARP cleavage and increased LC3B expression at 10 and 20 μM (after 48 h) and time-dependent up-regulation of these markers over 3 to 48 h at 20 μM^[2].
Artocarpin (20 μM; 12-48 h) induces G1 phase cell cycle arrest followed by apoptotic cell death in HT29 human colon adenocarcinoma cells when treated at 20 μM for 12, 24, 36, or 48 h^[2].
Artocarpin (6.7 μM) potently inhibits melanin biosynthesis in B16 melanoma cells with an IC₅₀ of 6.7 μM, without inducing cytotoxicity and without inhibiting tyrosinase activity^[3].
Artocarpin displays weak but relatively broad in vitro cytotoxicity against A549, MCF-7, 1A9, HCT-8, U-87-MG, MDA-MB-231, KB, and KB-VIN human tumor cell lines with ED₅₀ values ranging from 3.2 to 3.8 μg/mL, and shows inactive cytotoxicity against CAKI-1, SK-MEL-2, and PC-3 cell lines^[4].
Artocarpin (tested across a concentration range; 20 h with LPS) inhibits nitric oxide production in LPS-activated RAW264.7 mouse macrophage cells with an IC₅₀ of 18.7 μM^[5].
Artocarpin (2-20 μg/mL; 5 min-24 h) exerts rapid, concentration-dependent bactericidal activity against S. aureus ATCC 29213, with up to a ~4.8 log₁₀ cfu/mL reduction at 10× MIC within 1 h and no regrowth after 24 h^[6].
Artocarpin (10 μg/mL; 24 h) potently clears intracellular S. aureus ATCC 29213 in J774 macrophages, reducing bacterial load by ~3.25 log₁₀ cfu/mL at 5× MIC after 24 h of treatment^[6].
Artocarpin (5-10 μg/mL; 30 min-1 h) disrupts the membrane integrity of S. aureus ATCC 29213, causing rapid cellular lysis, reduced intracellular ATP, and increased extracellular ATP at 2.5× and 5× MIC^[6]. In Vivo:Artocarpin (100 mg/kg; p.o.; daily; 16 weeks) reduces colonic neoplasm multiplicity by 56% and improves survival in a mouse colitis-associated colorectal tumorigenesis model, while inhibiting PI3K/Akt pathway activation^[2].
Artocarpin (AH-5) (50 mg/kg; i.p.; two doses 3 hours apart) significantly reduces S. aureus ATCC 29213 bacterial load in neutropenic murine thigh tissue by ~0.6 log₁₀ cfu/g^[6].
Artocarpin (AH-5) (1%; topical; twice daily; 4 days) significantly reduces S. aureus ATCC 29213 bacterial load in murine skin tissue by ~1.0 log₁₀ cfu/g^[6].
Artocarpin (25-100 mg/kg; p.o.) exhibits dose-dependent anti-inflammatory activity in Wistar albino rats, with 100 mg/kg producing comparable inhibition to indomethacin 10 mg/kg in acute edema models and significant granuloma reduction^[7].
Artocarpin (25-100 mg/kg; p.o.) exhibits dose-dependent analgesic activity in Swiss albino mice, with 100 mg/kg producing comparable inhibition to diclofenac 10 mg/kg in formalin-induced paw licking and significant writhing reduction in acetic acid-induced writhing^[7].