The effect of indatraline on angiogenesis suppression through HIF-1α-mediated VEGF inhibition.

The present research reports a novel biological activity of indatraline, a compound clinically used as an antidepressant. We previously identified indatraline as an autophagy inducer. Autophagy is an intracellular catabolic pathway for degrading or recycling unnecessary organelles in response to cellular stress. Indatraline-mediated autophagy induction results from mTOR inhibition. The mTOR is a negative regulator of autophagy as well as a master regulator of angiogenesis. Angiogenesis defines the process by which new vessels are formed from pre-existing vascular tissues, providing nutrients to cancer cells, allowing rapid tumor progression. Accordingly, targeting angiogenesis to prevent cancer is an attractive therapeutic strategy. Here, we demonstrate that indatraline possibly acts to suppress tumor-mediated angiogenesis via downregulation of HIF-1α-mediated VEGF expression. The effects of indatraline on autophagy and angiogenesis could make it a potential drug candidate toward cancer treatment.