Cucurbitacin B exerts anti-cancer activities in human multiple myeloma cells in vitro and in vivo by modulating multiple cellular pathways
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Tai Yang1,2,*, Jin Liu2,*, Mali Yang2,*, Ning Huang3, Yueling Zhong1, Ting Zeng2, Rong Wei2, Zhongjun Wu2, Cui Xiao2, Xiaohua Cao2, Minhui Li2, Limei Li2, Bin Han4, Xiaoping Yu4, Hua Li5, Qiang Zou2
1School of Pharmacy, Chengdu Medical College, Chengdu, China
2Department of Immunology, Chengdu Medical College, Chengdu, China
3Laboratory for Aging Research, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China
4Department of Public Health, Chengdu Medical College, Chengdu, China
5Cancer Center, Chengdu Military General Hospital, Chengdu, China
*These authors have contributed equally to this work
Tai Yang, email: [email protected]
Qiang Zou, email: [email protected]
Keywords: cucurbitacin B, multiple myeloma, Aurora A kinase, multiple cellular pathways, xenograft
Received: March 07, 2016 Accepted: June 30, 2016 Published: July 13, 2016
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.
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