title: Synergistic effect of cucurbitacin B in combination with curcumin via enhancing apoptosis induction and reversing multidrug resistance in human hepatoma cells.
abstract: Cucurbitacin B is a plant-derived tetracyclic triterpenoid, which has been used for a variety of cancers, especially human hepatoma. Curcumin, isolated from a plant Curcuma longa also has found the anti-tumor property. In the present study, the synergistic effect of cucurbitacin B and curcumin was studied on BEL7402/5-Fu cells in vitro and BEL7402 tumor-bearing mice in vivo. The synergistic anticancer activity of these two compounds involves the two mechanisms. Firstly, curcumin synergistically enhanced the apoptosis of BEL7402/5-Fu cells induced by cucurbitacin B in the optimal mass ratio of 2:1 (cucurbitacin B:curcumin). The mechanism may result from the cell arresting in different phases of cell cycles and the apoptotic change of ultrastructure in BEL7402/5-Fu cells. Secondly, curcumin reversed the multidrug resistance (MDR) caused by cucurbitacin B in the optimized concentration of 67.9μM (25μg/ml). The mechanism was associated with the P-gp reduction, ΔΨm collapse and mitochondrial colocalization in BEL7402/5-Fu cells. The findings were consistent with the changes of the body weight and tumor volume, caspase3 activation and ATP down-regulation in vivo. In conclusion, cucurbitacin B in the combination with curcumin could serve as a novel, promising approach for human hepatoma.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 110016 Shenyang, China; School of Pharmacy, Liaoning Medical University, 121001 Jinzhou, China.
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Sun
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 110016 Shenyang, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 110016 Shenyang, China.
authors.forename: Jiaying
authors.initials: J
authors.lastname: Zhou
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 110016 Shenyang, China.
authors.forename: Ziyuan
authors.initials: Z
authors.lastname: Huang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 110016 Shenyang, China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Hu
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 110016 Shenyang, China.
authors.forename: Mingxi
authors.initials: M
authors.lastname: Qiao
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 110016 Shenyang, China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Zhao
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 110016 Shenyang, China. Electronic address: chendawei@syphu.edu.cn.
authors.forename: Dawei
authors.initials: D
authors.lastname: Chen
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001692:Biological Transport / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D005472:Fluorouracil / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008113:Liver Neoplasms / Q000473:pathology*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D014315:Triterpenes / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014315:Triterpenes; C041246:cucurbitacin B; D000255:Adenosine Triphosphate; D053148:Caspase 3; D003474:Curcumin; D005472:Fluorouracil
keywords: Cucurbitacin B; Curcumin; Enhancing apoptosis induction; Reversing multidrug resistance; Synergy