A therapeutically relevant, 3,3'-diindolylmethane derivative NGD16 attenuates angiogenesis by targeting glucose regulated protein, 78kDa (GRP78)

Chemico-biological Interactions
Debasis NayakAnindya Goswami

Abstract

Angiogenesis remain a critical procedure for tumor progression and malignancy. Anticancer agents targeting angiogenic cascades have been proved to be an effective strategy in the field of cancer therapeutics. The current study aims to explore the mechanistic prevention of angiogenesis and cancer cell proliferation by 1,1'-β-d-glucopyranosyl-3,3'-bis(5-bromoindolyl)-octyl methane (NGD16), a novel N-glycosylated derivative of 3,3'-diindolylmethane (DIM). NGD16 suppressed the viability of prostate cancer (PC-3), pancreatic adenocarcinoma (MiaPaca-2), colorectal cancer (COLO-205) and human umbilical vein endothelial cells (HUVECs) effectively with IC50 values 0.8 μM, 2.8 μM, 5.3 μM and 2.5 μM respectively. Abrogation of angiogenesis by NGD16 was promising in in vivo mouse Matrigel plug assay as well as in ex vivo sprouting of rat thoracic aorta. At the molecular level, NGD16 inhibited the expression of glucose regulated protein, 78 kDa (GRP78), vascular endothelial growth factor receptor-2 (VEGFR2) and matrix metalloproteinase-9 (MMP-9) expression, the main mediators of angiogenesis and neovessel formation. Overexpression of GRP78 upregulated the expression of MMP-9 and VEGFR2 in PC-3 and HUVECs. Antibody blocking of GRP78 further ...Continue Reading

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Citations

Jan 8, 2017·Bioorganic & Medicinal Chemistry·Carla GrossoTeresa M D V Pinho E Melo
Jun 9, 2019·Breast Cancer Research and Treatment·Debasis NayakAnindya Goswami

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