Studies On Anti-tumor And Anti-oxidative Effects Of Thymopentin (TP5)

Thymopentin (Arg-Lys-Asp-Val-Tyr, TP5) has shown immuno-regulatory activities in human beings. In the present study, we investigated the effects of TP5 combined with chemotherapeutic agents (DMSO or ADM) on the proliferation and differentiation of two human leukemia cell lines (HL-60 and K562). The anti-proliferation and differentiating effects induced by TP5 and DMSO (or ADM) were determined by cell viability, Wright's-Giemsa staining, and NBT-reduction activity. The percentage of apoptosis cells and the expression of Bcl-2 and CD95 were analysed by flow cytometry (FCM). The results showed that TP5 and DMSO displayed concentration-dependent inhibitory effects on the proliferation of HL-60 cells. TP5 could induce differentiation of HL-60 cells and enhance the effect when combined with DMSO. TP5 (500μmol/L) and DMSO (2%) induced apoptosis in HL-60 cells. In addition, TP5 could inhibit proliferation and induce differentiation of K562 cells and enhance the effects when combined with ADM. The significant morphology changes were observed when K562 cells were exposed to TP5 and ADM. All the results indicated that TP5 not only act as an immunomodulatory factor in cancer chemotherapy, but also could be a potential chemotherapeutic agent in the human leukemia therapy.We also investigated the protective effect of TP5 on myocardial injury induced by hydroxyl free radical in rats. The hydroxyl free radical was generated by the Fenton system established by FeSO₄ / H₂O₂. The cell viability of cardiac myocyte was determined by MTT assay. The result indicated that TP5 significantly attenuated myocardial injury induced by the Fenton system. The protection effect of TP5 was possibly via scavenging hydroxyl free radical.We studied the protective effect of TP5 on cultured PC12 cells injured by hydrogen peroxide. PC12 cells were pretreated with different concentrations of TP5 for 2 hours, then, treated with H₂O₂ (0.5mmol/L) for 48h. The cell survival rate (MTT assay) was measured. The data indicated that TP5 can strikingly and dose-dependently attenuated cell injury induced by H₂O₂. Our results suggest that TP5 may play an important role in neuron system repairing.