LXR-α/ABCA1 PAIR ENHANCES AND DEREGULATES VEGF MODULATED BY DIOSGENIN IN LIVER CANCER CELL LINE (HUH-7)

Author(s): Nithya Ganesan, Devan Umapathy and Antony Joseph Velanganni Arockiam

Abstract: The nuclear liver x receptor (LXR) is an important regulator for the cholesterol, fatty acids and glucose homeostasis level in the human body. LXRs also play an essential role in the enlargement and progression of liver cancer. We study the effect of diosgenin on angiogenesis in vivo by chorioallantoic membrane (CAM) assay. Diosgenin stimulates the expression of LXR-α and its target ATP-binding cassette transporter (ABCA1) gene in Huh-7 cells. Diosgenin upregulates LXR-α and ABCA1 protein regulates angiogenesis and downregulates HIF1-α and VEGF in Huh-7 cells. Our study suggested that activation LXR interferes with angiogenesis through the stimulation of LXR-αand its target gene ABCA1, which in turn suppresses HIF1-α and VEGF signaling, an essential pathway regulating angiogenesis. An unrecognized role of the LXR was pointed out by the observation of LXR-α as an ABCA1 target gene in vascular biology. In conclusion, LXR-α may be a potential curative target for tumor angiogenesis.

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