Effect of HM910, a novel camptothecin derivative, on the inhibition of multiple myeloma cell growth in vitro and in vivo.

Despite a variety of novel therapeutic agents, such as bortezomib, thalidomide and topotecan, multiple myeloma (MM) remains an incurable disease, thus the development of new chemotherapeutical agents is of high priority. We found HM910, a novel camptothecin (CPT) derivative, exhibited potent inhibition of MM cell growth in vitro and in xenografts of nude mice. Mechanistically, HM910 reduced the mitochondrial transmembrane potential (ΔΨm) via an increase in reactive oxygen species (ROS), which eventually resulting in the release of cytochrome c and the activation of mitochondrial-dependent apoptotic pathway. On the other hand, HM910 significantly triggered cell cycle arrest in G1 phase via downregulating the expressions of cyclin dependent kinase (CDK) 4 and 6, resulting in down-regulation of cyclin D1. Therefore, HM910 maybe a promising candidate for treating MM patients and is currently in phase I clinical trial in China.