Kumatakenin

Kumatakenin is an orally active apoptosis inducer and autophagy inhibitor, with a K_d value of 2.94 μM for mouse ATG5. Kumatakenin increases the activities of caspase-3, caspase-8 and caspase-9, thereby inducing caspase-dependent apoptosis in ovarian cancer cells. Kumatakenin reduces the expression of chemokines and pro-oncogenic factors in ovarian cancer cells, and inhibits M2 macrophage polarization. Kumatakenin inactivates TRIM65 function, reduces the expression and stability of FASN, and thus inhibits the proliferation, migration, invasion and tumor progression of esophageal cancer cells. Kumatakenin interacts with ATG5 to reduce its protein level, decrease LC3 level, and reduce the number of autophagosomes in the hippocampus. Kumatakenin binds to Eno3 to upregulate its expression, reduce the stability and expression level of IRP1 mRNA, inhibit ferroptosis, alleviate intestinal inflammation, and restore epithelial barrier function. Kumatakenin enhances the efficacy of antibiotics against pathogenic bacteria, inhibits SARS-CoV-2 replication, and reduces cytokine production. Kumatakenin is applicable to research related to ovarian cancer, esophageal cancer, depression and colitis^{[1][2][3][4][5]}. IC50 & Target:IC50: apoptosis^[1] In Vitro:Kumatakenin (0-100 μM; 48 h) induces dose-dependent inhibition of cell growth in human A2780 and SKOV3 ovarian cancer cells^[1].
Kumatakenin (0-30 μM; 48 h) increases the proportion of sub-G1 phase cells, a marker of cell death, in human SKOV3 ovarian cancer cells without inducing cell cycle arrest. It triggers apoptotic cell death mediated by caspase-3 activation, and induces dose-dependent activation of caspase-3, caspase-8 and caspase-9^[1].
Kumatakenin (0-30 μM; 24 h) dose-dependently downregulates the mRNA expression and secretion of MCP-1 and RANTES in human SKOV3 ovarian cancer cells^[1].
Kumatakenin (0-40 μM; 24 h) dose-dependently reduces the mRNA and protein expression of M2 macrophage markers CD206 and Trem-2 in THP-1-derived tumor-associated macrophages (TAMs), decreases the mRNA expression of pro-tumor factors IL-10, VEGF, MMP-2 and MMP-9, reduces the protein expression levels of MMP-2 and MMP-9, and inhibits the secretion of IL-10 and VEGF^[1].
Kumatakenin (0-40 μM; 12 h) dose-dependently reduces the mRNA expression levels of TRIM65 and FASN in KYSE410, TE-1, TE-10 and Case17 esophageal cancer cells^[2].
Kumatakenin (0-40 μM; 12 h) inhibits the co-expression of TRIM65 and FASN in KYSE410, TE-1, TE-10 and Case17 esophageal cancer cells^[2].
Kumatakenin (0-40 μM; 12 h) reduces the migration and invasion abilities of KYSE410, TE-1, TE-10 and Case17 esophageal cancer cells and downregulates the expression of pro-EMT markers in a dose-dependent manner, while upregulating the expression of anti-EMT markers after 12 h of treatment^[2].
Kumatakenin (0-40 μM; 24 h) reduces palmitic acid (PA) (HY-N0830) and oleic acid (OA) (HY-N1446)-induced triglyceride accumulation in KYSE410 and TE-1 esophageal cancer cells in a dose-dependent manner after 24 h of co-treatment, and decreases intracellular lipid deposition and TRIM65 expression^[2].
Kumatakenin (40 μM; 24 h) reduces the level of de novo palmitate synthesis from glucose in KYSE410 and TE-1 esophageal cancer cells^[2].
Kumatakenin (40 μM) inhibits TRIM65-mediated K63-linked polyubiquitination of FASN in TRIM65-reconstituted KYSE410 and TE-1 esophageal cancer cells^[2].
Kumatakenin (40-80 μM) reduces TRIM65-mediated K63-linked polyubiquitination of FASN in PA-treated, TRIM65-reconstituted KYSE410 and TE-1 esophageal cancer cells^[2].
Kumatakenin (6.25-100 μM) binds to purified ATG5 protein with a K_d of 2.94×10^-6 M^[3].
Kumatakenin (1-20 μM) reverses the loss of HT-22 cell viability induced by Corticosterone (CORT) (HY-B1618) and regulates the expression levels of autophagy-related proteins in HT-22 cells (upregulating P62, downregulating ATG5 and LC3), but these effects are abrogated by ATG5 overexpression^[3].
Kumatakenin (10-80 μM; 48 h) increases the viability of MODE-K mouse colonic epithelial cells treated with Erastin (HY-15763), reduces the level of lipid ROS in the cells, decreases intracellular iron levels and increases IRP1 protein levels, and accelerates the degradation rate of IRP1 mRNA in the cells in an Eno3-dependent manner^[5]. In Vivo:Kumatakenin (p.o.; once daily; for 22 consecutive days; 80 mg/kg) significantly reduces the volume and weight of esophageal xenograft tumors in male Balb/c nude mice^[2].
Kumatakenin (0.56-2.25 mg/kg) alleviates CORT-induced depressive-like behaviors in male C57BL/6J mice by reducing plasma CORT levels, increasing plasma 5-HT, DA and BDNF levels, downregulating the expression of ATG5 and LC3 to inhibit excessive autophagy in the hippocampus, and restoring hippocampal neuronal structure and BDNF levels^[3].
Kumatakenin (25-100 mg/kg; p.o.; once daily; for 9 consecutive days) significantly alleviates DSS (HY-116282C)-induced colitis in male C57BL/6 mice by upregulating Eno3 and modulating the Eno3-IRP1 axis to reduce cellular iron levels and inhibit ferroptosis in colonic epithelial cells^[5].