Supplementary kumatakenin prevents esophagus cancer progression by blocking TRIM65-FASN axis-mediated metabolic reprogramming

Esophageal carcinoma is a prevalent gastrointestinal malignancy worldwide. Effective treatment agents and procedures are crucial in the current global health problem. Kumatakenin (KM), a key ingredient in traditional Chinese medicinal cloves and Alpinia purpurata, has been widely explored for its therapeutic properties. However, Kumatakenin's oesophageal cancer inhibitory actions and pharmacological molecular mechanisms must be fully explored. The study found that knowledge management (KM) deactivated the E3 ubiquitin-protein ligase TRIM65 to decrease esophageal cancer cell proliferation and delay tumor development. The dosage-dependent suppression of esophageal cancer cell migration and invasion by KM was significant. Potassium monoxide (KM) reduced esophageal cancer growth in a well-established xenograft mouse model. High-throughput RNA sequencing and stable isotope labelling with amino acids in cell cultures (SILAC) were used to identify KM-induced gene dysregulation in esophageal cancer cells. TRIM65, a ubiquitinating enzyme, is essential to esophageal cancer growth. In addition, TRIM65 and FASN are linked in this syndrome. In addition, KM treatments reduced TRIM65 expression, FASN stability, and expression in esophageal cancer cells. Validating these findings in animal model tumor tissues confirmed them. The mechanistic investigation showed that TRIM65 directly connects with FASN in cancer cells, stabilizing FASN via K63-linked polyubiquitination. KM therapy disrupted interaction and stabilization mechanisms, according to this study. The enhanced stability of FASN in esophageal cancer cells enabled lipid synthesis and deposition. This enhanced cancer cell growth and tumor formation. Our findings show that upregulating TRIM65 increases cancer cell proliferation, migration, and invasion and reduces KM's suppressive effects on esophageal cancer. This study shows that TRIM65 inhibition is essential for KM's antineoplastic activities. The results of our study strongly suggest that knowledge management (KM) may treat esophageal cancer. This result comes from suppressing TRIM65-FASN signaling.