Demethoxycurcumin inhibits breast cancer vascular remodeling through RGS5 to delay the progression of breast cancer

In the occurrence and progression of breast cancer, tumor angiogenesis and metastasis play a central role. This indicates that anti-angiogenesis holds a significant position in anti-tumor therapy. Demethoxycurcumin is a bioactive diarylheptanoid compound extracted from Curcuma longa, a herb that serves both as food and medicine. As a member of the curcuminoid family, it exhibits anti-angiogenic and anti-tumor characteristics. But, the understanding of its potential mechanisms of action remains incomplete. Our experiments demonstrated that demethoxycurcumin significantly inhibited tumor growth (Ki67) and microvascular density (CD31) in the 4T1 breast cancer mouse model. Our in vitro experiments revealed that demethoxycurcumin inhibits the proliferation, migration, and angiogenesis of HUVECs in a dose-dependent manner. The underlying mechanism is characterized by a reduction in RGS5 expression in endothelial cells that proliferate as a consequence of tumor pathological features. The efficacy of high doses of demethoxycurcumin could be reversed by overexpression of RGS5, indicating that the effect of demethoxycurcumin is mediated through RGS5. These findings confirm that RGS5 is a key target for demethoxycurcumin in inhibiting angiogenesis in breast cancer, elucidating its anti-tumor mechanisms and providing new references for future research.