[CAS NO. 934593-90-5]  LW 6

LW6 inhibits HIF-1α expression induced by hypoxia. It promotes apoptosis preferentially in hypoxic cells. Treatment with LW6 presents no additive effect on cell cycle arrest. LW6 induces ROS formation through the depolarization of MMP in hypoxic cells. Although LW6 increases mitochondrial ROS production, the combination with hypoxia induces a marked increase in ROS production and this high level is maintained up until 24 h. LW6 is also a specific inhibitor of MDH2. As MDH2 is known to serve a significant role in the citric acid cycle at the mitochondrial membrane, LW6 indirectly reduces the activity of the mitochondrial respiratory chain through the inhibition of MDH2. In MDCKII-BCRP cells overexpressing BCRP, LW6 enhances significantly (p < 0.05) the cellular accumulation of mitoxantrone, a BCRP substrate, and is more potent than Ko143, a well-known BCRP inhibitor. In contrast to BCRP, LW6 has no inhibition effect on the functional activity and gene expression of P-gp. LW6 also down-regulates BCRP expression at concentrations of 0.1-10 μM. Furthermore, cells become more susceptible to the cytotoxicity of anticancer drugs in the presence of LW6.