Wogonoside exerts growth-suppressive effects against T acute lymphoblastic leukemia through the STAT3 pathway

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Abstract

Wogonoside is the main flavonoid of the traditional Chinese medicinal herb Scutellaria baicalensis Georgi and has been found to induce growth suppression in myelogenous leukemia cells. However, its activity in T acute lymphoblastic leukemia (T-ALL) is still unclear. In this study, T-ALL cell lines MOLT-3 and Jurkat were exposed to different concentrations of wogonoside for 48 h, and cell viability, cell cycle distribution, and apoptosis were measured. The involvement of signal transducers and activators of transcription 3 (STAT3) signaling in the activity of wogonoside was checked. The in vivo effect of wogonoside on T-ALL growth was investigated in a xenograft mouse model. Wogonoside significantly inhibited the viability of MOLT-3 and Jurkat cells, with the IC50 (the half maximal concentration) of 68.5 ± 3.8 and 52.6 ± 4.3 μM, respectively. However, healthy T lymphocytes were unaffected. Wogonoside-treated Jurkat cells exhibited a G1-phase cell cycle arrest and significant apoptosis, which was coupled with inactivation of STAT3 signaling. Overexpression of constitutively active STAT3 reversed wogonoside-mediated growth suppression and apoptosis and restored the expression of cyclin D1, Mcl-1, and Bcl-xL. In vivo studies demonstrated that wogonoside retarded tumor growth and suppressed STAT3 phosphorylation in Jurkat xenografts. In conclusion, wogonoside suppresses the growth of T-ALL through the STAT3 pathway and may have therapeutic benefits in this disease.

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