title: Effect of HM910, a novel camptothecin derivative, on the inhibition of multiple myeloma cell growth in vitro and in vivo.
abstract: 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.
authors.affiliation: First Affiliated Hospital, Sun Yat-sen University Guangzhou 510080, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.affiliation: First Affiliated Hospital, Sun Yat-sen University Guangzhou 510080, China ; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Cancer Center, Sun Yat-sen University Guangzhou 510060, China.
authors.forename: Yudan
authors.initials: Y
authors.lastname: Ouyang
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Cancer Center, Sun Yat-sen University Guangzhou 510060, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Fangsheng Pharmaceuticals, Inc Changsha 410000, China.
authors.forename: Wenqiang
authors.initials: W
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Cancer Center, Sun Yat-sen University Guangzhou 510060, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Cancer Center, Sun Yat-sen University Guangzhou 510060, China.
authors.forename: Zhencong
authors.initials: Z
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Cancer Center, Sun Yat-sen University Guangzhou 510060, China.
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Cancer Center, Sun Yat-sen University Guangzhou 510060, China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Cancer Center, Sun Yat-sen University Guangzhou 510060, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Cancer Center, Sun Yat-sen University Guangzhou 510060, China.
authors.forename: Liwu
authors.initials: L
authors.lastname: Fu
keywords: HM910; Multiple myeloma; apoptosis; camptothecin derivative; cell cycle