Anticancer Role of PPARγ Agonists in Hematological Malignancies Found in the Vasculature, Marrow, and Eyes

Figure 6

Direct and indirect effects of PPAR $\gamma$ agonists on tumor and stromal cells. “Off-target” (PPAR$\gamma$-independent) effects of PPAR$\gamma$ agonists frequently occur when the agonists are used at high concentrations (much higher than needed to active PPAR$\gamma$ by ligand binding) and in response to electrophilic PPAR$\gamma$ agonists such as 15d-PGJ₂ and CDDO, which can promote covalent bond formation with cellular proteins in a redox-sensitive manner to modulate signal transduction pathways. PPAR$\gamma$ agonists have been shown to affect almost every stage of tumor progression from inhibition of uncontrolled tumor growth, induction of apoptosis, inhibition of tumor cell adhesion and invasion through stromal compartments into or out of the blood stream, and inhibition of tumor-associated angiogenesis. PPAR$\gamma$ agonists induce expression of tumor-inhibiting molecules such as CD36, the EC receptor for TSP-1, as well as promote the differentiation of tumor cells, which tends to reduce their invasive and metastatic capabilities. The schematic in this figure was adapted from [181].