BCI

BCI, as a selective dual-specificity phosphatase 6 (DUSP6) inhibitor, can inhibit tumor growth and macrophage inflammation.^[1].

In vitro, BCI (1-4μM; 24-72h) showed no cytotoxic effects on RAW264.7 cells and BMMs, respectively^[1]. BCI (2-4μM; 72h) had no obvious effect on cell cycle progression or apoptosis in BMMs^[1]. BCI (0-4μM; 6d) decreased the cell viability of Neuroblastoma (NB) cell lines SK-N-AS, KELLY, IMR-32 and LAN-1 in a dose-dependent manner^[2]. BCI (4μM; 24h) significantly increased the proportion of cells expressing cleaved caspase-3, indicating the activation of apoptosis in KELLY cells^[2]. BCI (5μM; 6h) markedly increased ERK1/2 phosphorylation and decreased total NCC and NCC surface expression in mDCT cells^[4].

In vivo, BCI (10mg/kg/d; i.p.; 5d) suppressed AKT activation and prevents tumor formation in mouse prostate^[3]. BCI (50, 100, and 200mg/kg/d; p.o.; 1 month) obviously increased the number of pNrf2-positive cells in periodontal tissue and mitigated the alveolar bone loss  in rats with chronic periodontitis and diabetes mellitus (CPDM)^[5].

References:

[1] Cai C, et al. BCI Suppresses RANKL-Mediated Osteoclastogenesis and Alleviates Ovariectomy-Induced Bone Loss. Front Pharmacol. 2021 Nov 1;12:772540.

[2] Thompson EM, et al. The cytotoxic action of BCI is not dependent on its stated DUSP1 or DUSP6 targets in neuroblastoma cells. FEBS Open Bio. 2022 Jul;12(7):1388-1405. 

[3] Duan S, et al. Loss of FBXO31-mediated degradation of DUSP6 dysregulates ERK and PI3K-AKT signaling and promotes prostate tumorigenesis. Cell Rep. 2021 Oct 19;37(3):109870.

[4] Feng X, et al. Aldosterone modulates thiazide-sensitive sodium chloride cotransporter abundance via DUSP6-mediated ERK1/2 signaling pathway. Am J Physiol Renal Physiol. 2015 May 15;308(10):F1119-27.

[5] Zhu C, et al. The therapeutic role of baicalein in combating experimental periodontitis with diabetes via Nrf2 antioxidant signaling pathway. J Periodontal Res. 2020 Jun;55(3):381-391.