Abrus agglutinin is a potent anti-proliferative and anti-angiogenic agent in human breast cancer

作者：Bhutia Sujit K^*; Behera Birendra; Das Durgesh Nandini; Mukhopadhyay Subhadip; Sinha Niharika; Panda Prashanta Kumar; Naik Prajna Paramita; Patra Samir K; Mandal Mahitosh; Sarkar Siddik; Menezes Mitchell E; Talukdar Sarmistha; Maiti Tapas K; Das Swadesh K; Sarkar Devanand; Fisher Paul B^*

来源：International Journal of Cancer, 2016, 139(2): 457-466.

DOI：10.1002/ijc.30055

• Abrus
• Akt
• apoptosis
• angiogenesis
• IGFBP-2
• ROS

Abrus agglutinin (AGG), a plant lectin isolated from the seeds of Abrus precatorius, has documented antitumor and immunostimulatory effects in murine models. To examine possible antitumor activity against breast cancer, we established human breast tumor xenografts in athymic nude mice and intraperitoneally administered AGG. AGG inhibited tumor growth and angiogenesis as confirmed by monitoring the expression of Ki-67 and CD-31, respectively. In addition, TUNEL positive cells increased in breast tumors treated with AGG suggesting that AGG mediates anti-tumorigenic activity through induction of apoptosis and inhibition of angiogenesis. On a molecular level, AGG caused extrinsic apoptosis through ROS generation that was AKT-dependent in breast cancer cells, without affecting primary mammary epithelial cells, suggesting potential cancer specificity of this natural compound. In addition, using HUVECs, AGG inhibited expression of the pro-angiogenic factor IGFBP-2 in an AKT-dependent manner, reducing angiogenic phenotypes both in vitro and in vivo. Overall, the present results establish that AGG promotes both apoptosis and anti-angiogenic activities in human breast tumor cells, which might be exploited for treatment of breast and other cancers.

• 出版日期2016-7-15