KAVA chalcone, Flavokawain A, inhibits urothelial tumorigenesis in the UPII-SV40T transgenic mouse model
Menée sur un modèle murin transgénique, cette étude montre que la flavokavaïne A, une substance chimique appartenant à la classe des chalcones et provenant du kava (une plante originaire du Pacifique), peut inhiber la tumorigenèse urothéliale
Flavokawain A (FKA) is the predominant chalcone identified from the kava plant. We have previously demonstrated that FKA preferentially inhibits the growth of p53 defective bladder cancer cell lines. Here we examined whether FKA could inhibit bladder cancer development and progression in vivo in the UPII-SV40T transgenic model that resembles human urothelial cell carcinoma (UCC) with defects in the p53 and the retinoblastoma (RB) protein pathways. Genotyped UPII-SV40T mice were fed orally with vehicle control (AIN-93M) or FKA (6 g /kg food; 0.6%) for 318 days starting at 28 days of age. More than 64% of the male mice fed with FKA-containing food survived beyond 318 days of age, whereas only about 38% of the male mice fed with vehicle control food survived to that age (p= 0.0383). The mean bladder weights of surviving male transgenic mice with the control diet versus the FKA diet were 234.6 ± 72.5 versus 96.1±69.4 mg (P=0.0002). FKA was excreted primarily through the urinary tract and concentrated in the urine up to 8.4
μmol/L, averaging about 38 times (males) and 15 times (females) more concentrated than in the plasma (P=0.0001). FKA treatment inhibited the occurrence of high-grade papillary UCC, a precursor to invasive urothelial cancer, by 42.1%. A decreased expression of Ki67, survivin and XIAP and increased expression of p27 and DR5 and number of TUNEL-positive apoptotic cells were observed in the urothelial tissue of FKA-fed mice. These results suggest a potential of FKA in preventing the recurrence and progression of non-muscle invasive UCC.