title: Cucurbitacin B exerts anti-cancer activities in human multiple myeloma cells in vitro and in vivo by modulating multiple cellular pathways.
abstract: Cucurbitacin B (CuB), a triterpenoid compound isolated from the stems of Cucumis melo, has long been used to treat hepatitis and hepatoma in China. Although its remarkable anti-cancer activities have been reported, the mechanism by which it achieves this therapeutic activity remains unclear. This study was designed to investigate the molecular mechanisms by which CuB inhibits cancer cell proliferation. Our results indicate that CuB is a novel inhibitor of Aurora A in multiple myeloma (MM) cells, arresting cells in the G2/M phase. CuB also inhibited IL-10-induced STAT3 phosphorylation, synergistically increasing the anti-tumor activity of Adriamycin in vitro. CuB induced dephosphorylation of cofilin, resulting in the loss of mitochondrial membrane potential, release of cytochrome c, and activation of caspase-8. CuB inhibited MM tumor growth in a murine MM model, without host toxicity. In conclusion, these results indicate that CuB interferes with multiple cellular pathways in MM cells. CuB thus represents a promising therapeutic tool for the treatment of MM.
authors.affiliation: School of Pharmacy, Chengdu Medical College, Chengdu, China.|Department of Immunology, Chengdu Medical College, Chengdu, China.
authors.forename: Tai
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Immunology, Chengdu Medical College, Chengdu, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Immunology, Chengdu Medical College, Chengdu, China.
authors.forename: Mali
authors.initials: M
authors.lastname: Yang
authors.affiliation: Laboratory for Aging Research, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Huang
authors.affiliation: School of Pharmacy, Chengdu Medical College, Chengdu, China.
authors.forename: Yueling
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Department of Immunology, Chengdu Medical College, Chengdu, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zeng
authors.affiliation: Department of Immunology, Chengdu Medical College, Chengdu, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wei
authors.affiliation: Department of Immunology, Chengdu Medical College, Chengdu, China.
authors.forename: Zhongjun
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Immunology, Chengdu Medical College, Chengdu, China.
authors.forename: Cui
authors.initials: C
authors.lastname: Xiao
authors.affiliation: Department of Immunology, Chengdu Medical College, Chengdu, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Cao
authors.affiliation: Department of Immunology, Chengdu Medical College, Chengdu, China.
authors.forename: Minhui
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Immunology, Chengdu Medical College, Chengdu, China.
authors.forename: Limei
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Public Health, Chengdu Medical College, Chengdu, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Han
authors.affiliation: Department of Public Health, Chengdu Medical College, Chengdu, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Yu
authors.affiliation: Cancer Center, Chengdu Military General Hospital, Chengdu, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Immunology, Chengdu Medical College, Chengdu, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zou
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology; D064096:Aurora Kinase A / Q000037:antagonists & inhibitors*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014315:Triterpenes / Q000008:administration & dosage* / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C508609:IL10 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014315:Triterpenes; C041246:cucurbitacin B; D016753:Interleukin-10; C576917:AURKA protein, human; D064096:Aurora Kinase A
keywords: Aurora A kinase; cucurbitacin B; multiple cellular pathways; multiple myeloma; xenograft