title: Cucurbitacin B synergistically enhances the apoptosis-inducing effect of arsenic trioxide by inhibiting STAT3 phosphorylation in lymphoma Ramos cells.
abstract: Arsenic trioxide (ATO) is a classic apoptosis-inducing agent used to treat acute promyelocytic leukemia. However, the therapeutic effect of ATO is limited in lymphoma, which resists apoptosis possibly due to inappropriate activation of STAT3. Therefore, combination of ATO and STAT3 inhibitor may be a potential strategy to treat lymphoma. Dramatically, Cucurbitacin B (CuB), an effective component of the dichloromethane extraction from Trichosanthes kirilowii Maxim, synergistically eliminated the apoptosis resistance of Burkitt's lymphoma Ramos cells to ATO by inhibiting the phosphorylation of STAT3, followed in turn by downregulation of Bcl-2 and upregulation of Bax. Furthermore, CuB and ATO in combination have no pro-apoptotic effect on normal lymphatic cells, indicating the absence of toxicity to hematological cells. This synergistic effect was further confirmed in nude murine lymphoma model, which exhibited significant apoptosis induction and tumor growth inhibition. Collectively, CuB synergistically enhances the apoptosis-inducing effect of ATO by inhibiting STAT3 phosphorylation in Ramos cells.
authors.affiliation: a Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer , Tianjin , China.|b Key Laboratory of Cancer Prevention and Therapy , Tianjin's Clinical Research Center for Cancer , Tianjin , China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Ding
authors.affiliation: a Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer , Tianjin , China.|b Key Laboratory of Cancer Prevention and Therapy , Tianjin's Clinical Research Center for Cancer , Tianjin , China.
authors.forename: Jiadong
authors.initials: J
authors.lastname: Chi
authors.affiliation: a Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer , Tianjin , China.|b Key Laboratory of Cancer Prevention and Therapy , Tianjin's Clinical Research Center for Cancer , Tianjin , China.
authors.forename: Xue
authors.initials: X
authors.lastname: Yang
authors.affiliation: a Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer , Tianjin , China.|b Key Laboratory of Cancer Prevention and Therapy , Tianjin's Clinical Research Center for Cancer , Tianjin , China.
authors.forename: Jian
authors.initials: J
authors.lastname: Hao
authors.affiliation: a Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer , Tianjin , China.|b Key Laboratory of Cancer Prevention and Therapy , Tianjin's Clinical Research Center for Cancer , Tianjin , China.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: a Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer , Tianjin , China.|b Key Laboratory of Cancer Prevention and Therapy , Tianjin's Clinical Research Center for Cancer , Tianjin , China.
authors.forename: Cuihong
authors.initials: C
authors.lastname: Zhu
authors.affiliation: a Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer , Tianjin , China.|b Key Laboratory of Cancer Prevention and Therapy , Tianjin's Clinical Research Center for Cancer , Tianjin , China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Wang
authors.affiliation: a Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer , Tianjin , China.|b Key Laboratory of Cancer Prevention and Therapy , Tianjin's Clinical Research Center for Cancer , Tianjin , China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Liu
authors.affiliation: a Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer , Tianjin , China.|b Key Laboratory of Cancer Prevention and Therapy , Tianjin's Clinical Research Center for Cancer , Tianjin , China.
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Niu
authors.affiliation: c Opening Cancer Laboratory , Tianjin Medical University Cancer Institute and Hospital , Tianjin , China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ji
authors.affiliation: d Department of Pharmacology , Basic Medical College, Tianjin Medical University , Tianjin , China.
authors.forename: Dan
authors.initials: D
authors.lastname: Chen
authors.affiliation: a Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer , Tianjin , China.|b Key Laboratory of Cancer Prevention and Therapy , Tianjin's Clinical Research Center for Cancer , Tianjin , China.
authors.forename: Xiongzhi
authors.initials: X
authors.lastname: Wu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide / Q000494:pharmacology; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy; D010766:Phosphorylation / Q000187:drug effects; D050796:STAT3 Transcription Factor / Q000187:drug effects / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D050796:STAT3 Transcription Factor; D014315:Triterpenes; C041246:cucurbitacin B; D000077237:Arsenic Trioxide
keywords: Burkitt’s lymphoma; Cucurbitacin B; Trichosanthes kirilowii Maxim; apoptosis; arsenic trioxide