Details

Autor(en) / Beteiligte

• Zhu, Hai-Yan
• Huang, Zong-Xuan
• Chen, Guo-Qi
• Sheng, Fen
• Zheng, Yin-Suo

Titel

Typhaneoside prevents acute myeloid leukemia (AML) through suppressing proliferation and inducing ferroptosis associated with autophagy

Ist Teil von

• Biochemical and biophysical research communications, 2019-09, Vol.516 (4), p.1265-1271

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2019

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• Leukemia remains a fatal disease for most patients and effective therapeutic strategies are urgently required. Typhaneoside (TYP) is a major flavonoid in the extract of Pollen Typhae, showing significant biological and pharmacological effects. In the present study, we explored the effects of TYP on acute myeloid leukemia (AML) progression. The results indicated that TYP markedly reduced the cell viability of AML cells and arrested the cell cycle at the G2/M phase by regulating the expression of associated proteins. In addition, TYP significantly induced apoptosis in AML cells by promoting the activation of Caspase-3. Intracellular and mitochondrial reactive oxygen species (ROS) accumulation were highly detected in AML cells after treatment with TYP. Moreover, TYP clearly induced ferroptosis in AML cells, and this process was iron-dependent and attendant with mitochondrial dysfunction. We also found that TYP significantly triggered autophagy in AML cells by promoting the activation of AMP-activated protein kinase (AMPK) signaling, contributing to ferritin degradation, ROS accumulation and ferroptotic cell death ultimately. In conclusion, the findings above provided solid evidences that TYP could be a promising therapeutic agent to prevent AML progression by inducing apoptosis, ROS production, autophagy and ferroptosis. •Typhaneoside arrested cell cycle at G2/M phase, induced apoptosis and ROS accumulation in AML cell lines.•Typhaneoside induces autophagy by improving AMPK pathway, contributing to autophagy dependent degradation of FTH in AML cells.•Typhaneoside suppresses tumor growth in a HL60 xenograft animal model.