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Article

Higenamine enhances the antitumor effects of cucurbitacin B in breast cancer by inhibiting the interaction of AKT and CDK2

  • Authors:
    • Zi-Qi Jin
    • Jian Hao
    • Xue Yang
    • Jing-Hua He
    • Jing Liang
    • Jin-Wei Yuan
    • Yu Mao
    • Dan Liu
    • Rui Cao
    • Xiong-Zhi Wu
    • Xin Li
    • Dan Chen
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, P.R. China, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, P.R. China, Department of Medical Oncology, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China, Zhong-Shan-Men Inpatient Department, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, P.R. China
  • Pages: 2127-2136
    |
    Published online on: August 6, 2018
       https://doi.org/10.3892/or.2018.6629
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Abstract

Cucurbitacin B (Cu B), a tetracyclic triterpenoid derived from Trichosanthes kirilowii Maxim, exhibits anticancer effects against various types of tumor. Higenamine, isolated from Radix Aconiti Lateralis Preparata, has been used as a dietary supplement for regulating metabolic function. The present study suggested that higenamine enhances Cu B-induced cytotoxicity in breast cancer cells and in vivo. Network pharmacology analysis was used to identify the possible mechanism of action. Cu B alone inhibited breast cancer cell growth, induced apoptosis, and arrested the cell cycle in the G2/M phase. Cu B combined with higenamine potentiated the cytotoxic effect of Cu B, resulting in the enhanced induction of apoptosis and G2/M arrest. The network pharmacology analysis also found that the major predicted targets of Cu B in breast cancer were AKT, endoplasmic reticulum, farnesyltransferase, CAAX box, α, platelet-derived growth factor receptor α, peroxisome proliferator-activated receptor, RET proto-oncogene, and vascular endothelial growth factor A. The possible targets of higenamine involved in the synergic action were cyclin A2, cyclin-dependent kinase 2 (CDK2), dihydrofolate reductase, and protein kinase CAMP‑activated catalytic subunit α. The associated pathways were summarized by Kyoto Encyclopedia of Genes and Genomes pathway analysis, and it was hypothesized that higenamine may enhance the antitumor effects of Cu B in breast cancer through inhibition of the interaction of AKT and CDK2. The protein expression was assayed by western blot analysis. The combined treatment also resulted in significant inhibition of growth in vivo.
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Copy and paste a formatted citation
Spandidos Publications style
Jin Z, Hao J, Yang X, He J, Liang J, Yuan J, Mao Y, Liu D, Cao R, Wu X, Wu X, et al: Higenamine enhances the antitumor effects of cucurbitacin B in breast cancer by inhibiting the interaction of AKT and CDK2. Oncol Rep 40: 2127-2136, 2018.
APA
Jin, Z., Hao, J., Yang, X., He, J., Liang, J., Yuan, J. ... Chen, D. (2018). Higenamine enhances the antitumor effects of cucurbitacin B in breast cancer by inhibiting the interaction of AKT and CDK2. Oncology Reports, 40, 2127-2136. https://doi.org/10.3892/or.2018.6629
MLA
Jin, Z., Hao, J., Yang, X., He, J., Liang, J., Yuan, J., Mao, Y., Liu, D., Cao, R., Wu, X., Li, X., Chen, D."Higenamine enhances the antitumor effects of cucurbitacin B in breast cancer by inhibiting the interaction of AKT and CDK2". Oncology Reports 40.4 (2018): 2127-2136.
Chicago
Jin, Z., Hao, J., Yang, X., He, J., Liang, J., Yuan, J., Mao, Y., Liu, D., Cao, R., Wu, X., Li, X., Chen, D."Higenamine enhances the antitumor effects of cucurbitacin B in breast cancer by inhibiting the interaction of AKT and CDK2". Oncology Reports 40, no. 4 (2018): 2127-2136. https://doi.org/10.3892/or.2018.6629
Copy and paste a formatted citation
x
Spandidos Publications style
Jin Z, Hao J, Yang X, He J, Liang J, Yuan J, Mao Y, Liu D, Cao R, Wu X, Wu X, et al: Higenamine enhances the antitumor effects of cucurbitacin B in breast cancer by inhibiting the interaction of AKT and CDK2. Oncol Rep 40: 2127-2136, 2018.
APA
Jin, Z., Hao, J., Yang, X., He, J., Liang, J., Yuan, J. ... Chen, D. (2018). Higenamine enhances the antitumor effects of cucurbitacin B in breast cancer by inhibiting the interaction of AKT and CDK2. Oncology Reports, 40, 2127-2136. https://doi.org/10.3892/or.2018.6629
MLA
Jin, Z., Hao, J., Yang, X., He, J., Liang, J., Yuan, J., Mao, Y., Liu, D., Cao, R., Wu, X., Li, X., Chen, D."Higenamine enhances the antitumor effects of cucurbitacin B in breast cancer by inhibiting the interaction of AKT and CDK2". Oncology Reports 40.4 (2018): 2127-2136.
Chicago
Jin, Z., Hao, J., Yang, X., He, J., Liang, J., Yuan, J., Mao, Y., Liu, D., Cao, R., Wu, X., Li, X., Chen, D."Higenamine enhances the antitumor effects of cucurbitacin B in breast cancer by inhibiting the interaction of AKT and CDK2". Oncology Reports 40, no. 4 (2018): 2127-2136. https://doi.org/10.3892/or.2018.6629
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