BV6, a SMAC mimetic, inhibits the inhibitors of apoptosis proteins (IAPs), causing apoptosis [1]. BV6 can induce degradation of IAPs, including cIAP1 and cIAP2, and sensitize the resistant cancer cell lines to apoptosis induced by the death ligands TNF-α and TRAIL [2]. BV6 has been widely used to inhibit the growth, clonal formation and angiogenesis of various cancer cells [3].
In vitro, BV6 treatment for 24 hours significantly inhibited the viability of MCF7 and MDA-MB-231 cells, with IC50 values of 5.36μM and 3.71μM [4]. Treatment with 10µM BV6 for 24 hours significantly attenuated the pro-inflammatory signaling induced by TNF and CD40L and triggered the maturation of immature monocyte-derived dendritic cells (iDCs)[5]. 2µM BV6 treatment for 48 hours significantly increased the mRNA and protein expression levels of caspase-3 and caspase-9, and decreased the expression level of LC3-II protein in NCI-H23 cells[6].
In vivo, BV6 treatment via a single intraperitoneal injection at a dose of 10mg/kg significantly inhibited the inflammatory state of endometriosis-like lesions in mice within 4 weeks, and reduced the expression of NF-κB p65 and phosphorylated NF-κB p65[7]. A single intraductal injection of 0.1mg dose of BV6 into the gallbladder significantly induced intrahepatic bile duct injury and inflammatory response in mice within 5 days[8].
References:
[1] Li W, Li B, Giacalone N J, et al. BV6, an IAP antagonist, activates apoptosis and enhances radiosensitization of non-small cell lung carcinoma in vitro[J]. Journal of Thoracic Oncology, 2011, 6(11): 1801-1809.
[2] El-Mesery M, Shaker M E, Elgaml A. The SMAC mimetic BV6 induces cell death and sensitizes different cell lines to TNF-α and TRAIL-induced apoptosis[J]. Experimental Biology and Medicine, 2016, 241(18): 2015-2022.
[3] Nikkhoo A, Rostami N, Farhadi S, et al. Codelivery of STAT3 siRNA and BV6 by carboxymethyl dextran trimethyl chitosan nanoparticles suppresses cancer cell progression[J]. International journal of pharmaceutics, 2020, 581: 119236.
[4] Rafat S, Singh P, Pandey K K, et al. SMAC mimetic BV6 Co-treatment downregulates the factors involved in resistance and relapse of cancer: IAPs and autophagy[J]. Biology, 2022, 11(11): 1581.
[5] Müller-Sienerth N, Dietz L, Holtz P, et al. SMAC mimetic BV6 induces cell death in monocytes and maturation of monocyte-derived dendritic cells[J]. PLoS One, 2011, 6(6): e21556.
[6] Beg M M A, Saxena A, Singh V K, et al. Modulatory role of BV6 and chloroquine on the regulation of apoptosis and autophagy in non-small cell lung cancer cells[J]. Journal of Cancer Research and Therapeutics, 2023, 19(Suppl 1): S341-S348.
[7] Taniguchi F, Uegaki T, Nakamura K, et al. Inhibition of IAP (inhibitor of apoptosis) proteins represses inflammatory status via nuclear factor‐kappa B pathway in murine endometriosis lesions[J]. American Journal of Reproductive Immunology, 2018, 79(1): e12780.
[8] Guicciardi M E, Krishnan A, Bronk S F, et al. Biliary tract instillation of a SMAC mimetic induces TRAIL-dependent acute sclerosing cholangitis-like injury in mice[J]. Cell death & disease, 2018, 8(1): e2535-e2535.