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Updated: Nov 17, 2025
HUVEC Tube-formation Assay to Evaluate the Impact of Natural Products on Angiogenesis
Published on: June 24, 2019
Antiangiogenic effect of arsenic trioxide in HUVECs by FoxO3a-regulated autophagy
Zhuo Sun1, Yidan Cao1, Yueping Xing1
1Department of Pathology, Laboratory of Clinical and Experimental Pathology, Xuzhou Medical University, Xuzhou, China.
Abstract:
Arsenic trioxide (ATO) has been shown to have antitumor effect in different tumors, although the underlying mechanisms are not fully understood. Autophagy plays a critical role in tumorigenesis and cancer therapy and has been found to be activated by ATO in different cells. However, the role of autophagy in the antitumor effect of ATO has not yet been elucidated. In this study, we investigated the role of autophagy in the antiangiogenic effect of ATO in human umbilical vein endothelial cells (HUVECs) in vitro and its underlying mechanism. Our data showed that ATO suppresses angiogenesis and induces autophagy in HUVECs through upregulation of forkhead box protein O3 (FoxO3a). Co-incubated with autophagy inhibitor or knockdown of FoxO3a effectively inhibited ATO-induced autophagy and reversed the antiangiogenic effect of ATO, indicating that ATO-induced autophagy plays an antiangiogenic role in HUVECs. Our results highlight the importance of autophagy in the antiangiogenic effect of ATO and provide an improved understanding of the function of ATO.
Insights
Arsenic trioxide (ATO) inhibits blood vessel formation by inducing autophagy, a cellular process. This antiangiogenic effect is mediated by the upregulation of forkhead box protein O3 (FoxO3a) in endothelial cells.
Area of Science:
- Oncology
- Cell Biology
- Molecular Medicine
Background:
- Arsenic trioxide (ATO) exhibits antitumor properties, but its mechanisms remain unclear.
- Autophagy is implicated in cancer development and treatment and is activated by ATO.
- The specific role of autophagy in ATO's antitumor effects requires further investigation.
Purpose of the Study:
- To investigate the role of autophagy in the antiangiogenic effects of ATO.
- To elucidate the underlying molecular mechanisms in human umbilical vein endothelial cells (HUVECs).
Main Methods:
- In vitro study using HUVECs.
- Assessment of angiogenesis suppression and autophagy induction by ATO.
- Upregulation of forkhead box protein O3 (FoxO3a) was analyzed.
- Intervention with autophagy inhibitors and FoxO3a knockdown.
Main Results:
- ATO significantly suppressed angiogenesis in HUVECs.
- ATO induced autophagy in HUVECs, correlating with FoxO3a upregulation.
- Inhibition of autophagy or FoxO3a knockdown reversed the antiangiogenic effect of ATO.
Conclusions:
- ATO-induced autophagy plays a critical antiangiogenic role in HUVECs.
- The forkhead box protein O3a (FoxO3a) pathway is essential for ATO's antiangiogenic mechanism.
- This study enhances the understanding of ATO's function in cancer therapy.
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