BV6

BV6 is an antagonist of cIAP1 and XIAP, members of the inhibitors of apoptosis (IAP) family. IC50 & Target: IAP^[1] In Vitro: HCC193 has an IC₅₀ of 7.2 μM in MTS assays, while H460 cells are not reduced to 50% viability even with 30 μM BV6 treatment. Administration of 1 μM BV6 to HCC193 cells induces complete depletion of cIAP1 levels at 1 hour post-treatment, while a decrease in XIAP levels is not seen until 24 hours following addition of drug. Similarly, 5 μM BV6 fully depletes cIAP1 at 1 hour and begin to reduce XIAP at 24 hours in H460 cells. In parallel findings, cIAP1 levels are decreased in response to a small dose of 0.25 μM BV6 in both cell lines, whereas trace amounts of XIAP are still present at 5μM BV6. HCC193 cells demonstrates noticeable cleaved caspase-3 levels beginning 12 hours post-incubation with 1μM BV6, and cleaved caspase-3 levels continued to increase in a time-dependent manner over 48 hours. Treatment of HCC193 cells with 1 μM BV6 for 24 hours causes a significant survival curve shift in HCC193 cells relative to DMSO-treated cells, with a DER=1.38 (p<0.05)^[1]. BV6 (2 and 5 µM) significantly represses BrdU incorporation in ectopic and eutopic (disease-free and myomas) ESCs. An ~30% decrease of BrdU incorporation is observed in both groups after treatment with 5 µM BV6^[2]. In Vivo: Murine cIAP-1, cIAP-2 and XIAP expressions are clearly observed in the cytoplasm of both epithelial and stromal cells of implants, whereas Survivin is mainly expressed in the nuclei BV6 treatment for 4 weeks attenuated the intensity of IAPs expression. The size of lesions range from ~2 to 7 mm in diameter. The monolayer epithelial cell lining of the cyst is shown. After immunohistochemical staining, cytokeratin and vimentin are positively stained, whereas calretinin is negative. After BV6 treatment for 4 weeks, the total number of lesions (4.6 versus 2.8/mouse), the average weight (78.1 versus 32.0 mg/mouse) and the surface area (44.5 versus 24.6 mm²/mouse) of lesions are significantly less than in the controls. In the endometrial gland epithelia or stroma, the percentage of Ki67-positive cells decreases after BV6 treatment^[2].