Objective: Taspine, isolated from Radix et Rhizoma Leonticis has demosntrated potential proctiective effectsagainst cancer. Tas13D, a novel taspine derivative synthetized by structure-based drug design, have been shownto possess interesting biological and pharmacological activities. The current study was designed to evaluateits antiproliferative activity and underlying mechanisms.
Methods: Antiproliferative activity of tas13D wasevaluated by xenograft in athymic mice in vivo, and by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazoliumbromide (MTT) and cell migration assays with human liver cancer (SMMC-7721) cell lines in vitro. Dockingbetween tas13D and VEGFR and EGFR was studied by with a Sybyl/Surflex module. VEGF and EGF andtheir receptor expression was determined by ELISA and real-time PCR methods, respectively.
Results: Ourpresent study showed that tas13D inhibited SMMC-7721 xenograft tumor growth, bound tightly with the activesite of kinase domains of EGFR and VEGFR, and reduced SMMC-7721 cell proliferation (IC=34.7 μmol/L)and migration compared to negative controls. VEGF and EGF mRNAs were significantly reduced by tas13Dtreatment in a dose-dependent manner, along with VEGF and EGF production.
Conclusion: The obtained resultssuggest that tas13D inhibits tumor growth and cell proliferation by inhibiting cell migration, downregulatingmRNA expression of VEGF and EGF, and decreasing angiogenic factor production. Tas13D deserves furtherconsideration as a chemotherapeutic agent.