PBOX 6 is a pyrrolo-1,5-benzoxazepine (PBOX) compound exhibiting anticancer and antitumor activity by inhibiting breast cancer cell growth in vitro and selectively inducing apoptosis in leukemia cells through c-Jun NH2 terminal kinase-dependent phosphorylation and inactivation of Bcl-2 and Bcl-XL.

PBOX 6, a potent apoptotic PBOX, does not elicit a general toxic effect in a rat R2C Leydig cell line. Treatment with PBOX 6 (0-25 μM, 16 h) induces dose- and time-dependent apoptosis and causes DNA fragmentation at 10 μM in HL-60 cells. Additionally, PBOX 6 (10 μM) induces apoptosis through the activation of caspase 3-like proteases in HL-60 cells. The apoptotic induction by PBOX 6 (10 μM) also leads to the accumulation of cytochrome c in the cytosol, independent of oxidative stress, peripheral-type benzodiazepine receptor (PBR), and NF-κB[1]. In MCF-7 cells, PBOX 6 (25 μM) induces apoptosis through the activation of caspase-7[3]. Furthermore, in K562 cells, PBOX 6 (10 μM) induces the redistribution of cypA from the nucleus to the cytosol and nucleocytoplasmic redistribution of cypA and pin1 through a JNK-dependent manner. This effect is also dependent on upstream activation of a trypsin-like serine protease, correlating with G2/M arrest[2].