A promising antitumor activity of evodiamine incorporated in hydroxypropyl-beta-cyclodextrin: pro-apoptotic activity in human hepatoma HepG2 cells

作者：Qiu, Chao; Gao, Li-Na; Yan, Kuo; Cui, Yuan-Lu^*; Zhang, Ye

来源：Chemistry Central Journal, 2016, 10(1): 46.

DOI：10.1186/s13065-016-0191-y

• Evodiamine
• Hydroxypropyl-beta-cyclodextrin
• Apoptosis
• Antitumor
• P-glycoprotein

Background: Evodiamine has gained wide interests recently because of its antitumor activities. However, a superior bioavailability is required to achieve better efficacy due to its poor water solubility. The aim of this study was to enhance the evodiamine's aqueous solubility by preparing evodiamine/hydroxypropyl-beta-cyclodextrin (EVO/HP-beta-CD) inclusion complex, which is incorporated evodiamine into HP-beta-CD, and compare the antitumor activities before and after inclusion with HP-beta-CD in human hepatoma HepG2 cells.
Results: The EVO/HP-beta-CD inclusion complexes were prepared by the kneading method and structurally characterized. P-glycoprotein ATPase assays firstly demonstrated that evodiamine was a substrate of P-glycoprotein, while HP-beta-CD and EVO/HP-beta-CD inclusion complexes inhibited P-glycoprotein by blocking P-glycoprotein ATPase activity. The EVO/HP-beta-CD inclusion complexes may be a promising anticancer drug candidate without drug resistance. After given evodiamine or EVO/HP-beta-CD inclusion complexes intervention, cell viability evaluation indicated that the half inhibition concentration of evodiamine and EVO/HP-beta-CD inclusion complexes on HepG2 cells was 8.516 and 0.977 mu M, respectively. The caspase-3 enzyme activity analysis and Annexin V/PI double-staining revealed that EVO/HP-beta-CD inclusion complexes possessed better antitumor activities than evodiamine. Additionally, Hoechst 33258 staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling assay demonstrated that EVO/ HP-beta-CD inclusion complexes induced HepG2 cell apoptosis more effectively than evodiamine.
Conclusions: The improved antitumor activities of evodiamine were attributed to the enhanced solubility and P-glycoprotein inhibition by HP-beta-CD. These results are promising for the drug administration of EVO/HP-beta-CD inclusion complexes to enhance the bioavailability of evodiamine in vivo.

• 出版日期2016-7-25
• 单位天津中医药大学