Modulation of glycolysis and lipogenesis by novel PI3K selective molecule represses tumor angiogenesis and decreases colorectal cancer growth.

Phosphatidylinositol 3-kinase (PI3K) pathway drives cancer progression through direct regulation of most oncogenic properties. Here, we report that PI3K pathway signaling up-regulates cancer cell proliferation, metastasis and angiogenesis through modulation of cancer metabolism. These oncogenic metabolic processes were disrupted, by a novel PI3K inhibitor, 3-Dihydro-2-(naphthalene-1-yl) quinazolin-4(1H)-one (DHNQ) in colon cancer cells. DHNQ inhibited the Warburg effect and lipid synthesis by reducing gene expression of glycolytic and lipogenesis regulatory enzymes. This downregulation at gene level by DHNQ inhibited metabolic flux to repress proliferation, migration and invasion characteristics of colon cancer. Furthermore, the metabolic attenuation caused repression of in vitro/in vivo angiogenesis providing new insights in PI3K regulated angiogenesis via metabolic alterations. Our results suggest that multifaceted targeting of oncogenic metabolism by their upstream PI3K regulatory signaling may be an effective cancer treatment approach.

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