Figure 6. Treatment with 1 inhibits tumor growth and decreases density of vasculature without induction of HIF-1a or expression of proangiogenic factors.

A) Compound 1 reduces microvessel density, hypoxia-related gene expression and cell proliferation, but does not increase HIF-1a levels. Presence of apoptosis in HIF-1a positive, but not HIF-1a negative areas, increased reliance of cancer cells on proximity to vasculature also indicate increased sensitivity of cancer cells to hypoxia. B) Therapies targeting angiogenesis that do not impair hypoxic adaptation (e.g. Anti-VEGF) can lead to increased expression of prometastatic and proangiogenic factors. Treatment with 1 inhibits expression of many of those factors, thus contributing to impaired adaptation of tumors to hypoxia.