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- W2327891839 abstract "Trichosanthin (TCS), a type I ribosome-inactivating protein (RIP-I) and renowned Chinese traditional medicine, displays a broad spectrum of biological and pharmacological properties. Particularly, its anti-tumor activity has received a great deal of attention. However, the cellular mechanism for TCS uptake varies with different tumor cell lines, leading to discrepancies in its reported ability to penetrate cells. In this study, HBD, a human derived cell-penetrating peptide (CPP), was used to improve the delivery of TCS into several types of tumor cells, including HeLa cells. Recombinant TCS (rTCS) with or without the fused HBD peptide was expressed in Escherichia coli cells and successfully purified by Ni-NTA affinity chromatography. The cellular uptake efficiency of FITC-labelled-rTCS-HBD was observed in HeLa cells and compared with the uptake efficiency of non-HBD conjugated rTCS under the same conditions using laser confocal microscopy. Moreover, the IC50 value of rTCS-HBD in the tested tumor cells was much lower than that of rTCS, indicating that HBD could efficiently deliver the rTCS into tumor cells. When compared with rTCS, rTCS-HBD induced higher rates of apoptosis in HeLa cells as analyzed by flow cytometry. Furthermore, the apoptotic events observed in HeLa cells incubated with HBD-fused rTCS included activation of Caspase-9, decrease in the Bcl-2/Bax ratio, and cleavage of PARP. These results strongly suggest the participation of mitochondria in apoptosis. This report illustrates one possible method for achieving the efficient transport of TCS into cells using a CPP as a vector, and increases the likelihood that TCS can be used in the clinic." @default.
- W2327891839 created "2016-06-24" @default.
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- W2327891839 date "2016-07-01" @default.
- W2327891839 modified "2023-10-16" @default.
- W2327891839 title "Enhanced anti-tumor activity of trichosanthin after combination with a human-derived cell-penetrating peptide, and a possible mechanism of activity" @default.
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- W2327891839 doi "https://doi.org/10.1016/j.fitote.2016.03.019" @default.
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