title: Synergistic action of 5Z-7-oxozeaenol and bortezomib in inducing apoptosis of Burkitt lymphoma cell line Daudi.
abstract: Treatment failure in cancer chemotherapy is largely due to the toxic effects of chemotherapeutic agents on normal cells/tissues. The proteasome inhibitor bortezomib has been successfully applied to treat multiple myeloma (MM), but there are some common adverse reactions in the clinic including peripheral neuropathy (PN). The TAK1 selective inhibitor 5Z-7-oxozeaenol has been widely studied in cancer therapy. Here, we investigated the potential synergy of bortezomib and 5Z-7-oxozeaenol in Burkitt's lymphoma (BL) cell lines. Cell viability assay showed that co-treatment of bortezomib at 8 nM, representing a one-eighth concentration for growth arrest, and 5Z-7-oxozeaenol at 2 μM, a dose that exhibited insignificant cytotoxic effects, synergistically induced apoptosis in the cell line Daudi. In parallel with the increasing dose of the bortezomib, and 5Z-7-oxozeaenol at 0.5 μM, lower colony formation efficiencies were seen in the cell line Daudi. Western blotting analysis verified that TAK1 inhibition by 5Z-7-oxozeaenol completely blocked JNK, p38, Erk, IKK, and IκB phosphorylation, which was almost instantly activated by TAK1 both directly or indirectly. Both agents synergistically prevented nuclear translocation of NF-κB, a characteristic of NF-κB inactivation. Moreover, a synergistic effect of bortezomib and 5Z-7-oxozeaenol on Western blotting analysis and flow cytometry was disclosed. Collectively, our results indicated that the proteasome inhibitor bortezomib and the TAK1 inhibitor 5Z-7-oxozeaenol displayed synergy on inhibiting BL cell apoptosis by inhibiting NF-κB activity.
authors.affiliation: Department of Hematology, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.|College of life sciences, Guizhou University, Guiyang, 550025, China.|Department of Stomatology, Huashan Hospital, Fudan University, Shanghai, 200040, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Hematology, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Hematology, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Ophthalmology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Jiayao
authors.initials: J
authors.lastname: Ou
authors.affiliation: Department of Ophthalmology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Rongbin
authors.initials: R
authors.lastname: Wei
authors.affiliation: Department of Ophthalmology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Junjun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Ophthalmology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Wenping
authors.initials: W
authors.lastname: Cai
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, 200040, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Stomatology, Huashan Hospital, Fudan University, Shanghai, 200040, China.
authors.forename: Shouliang
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Ophthalmology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Hematology, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Stomatology, Huashan Hospital, Fudan University, Shanghai, 200040, China. shangfengliufudan@163.com.
authors.forename: Shangfeng
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Hematology, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China. lab7182@tongji.edu.cn.
authors.forename: Aibin
authors.initials: A
authors.lastname: Liang
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D017209:Apoptosis; D000069286:Bortezomib / Q000008:administration & dosage*; D002051:Burkitt Lymphoma / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival; D003593:Cytoplasm / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000737:chemistry; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D061988:Proteasome Inhibitors / Q000008:administration & dosage; D051381:Rats; D015025:Zearalenone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000099151:MAP Kinase Kinase Kinase 7; D007783:Lactones; D012118:Resorcinols
chemical_list: D000970:Antineoplastic Agents; D000069286:Bortezomib; D004791:Enzyme Inhibitors; D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B; D061988:Proteasome Inhibitors; D015025:Zearalenone; D000099151:MAP Kinase Kinase Kinase 7; C505734:7-oxozeanol; D007783:Lactones; D012118:Resorcinols
keywords: 5Z-7-oxozeaenol; Bortezomib; Burkitt’s lymphoma; NF-κB; TAK1