Identification of Id1 as a downstream effector for arsenic-promoted angiogenesis via PI3K/Akt, NF-κB and NOS signaling

Chun-Hao Tsai; Ming-Hui Yang; Amos C Hung; Shou-Cheng Wu; Wen-Chin Chiu; Ming-Feng Hou; Yu-Chang Tyan; Yun-Ming Wang; Shyng-Shiou F Yuan

doi:10.1039/c5tx00280j

Identification of Id1 as a downstream effector for arsenic-promoted angiogenesis via PI3K/Akt, NF-κB and NOS signaling

Toxicol Res (Camb). 2015 Oct 5;5(1):151-159. doi: 10.1039/c5tx00280j. eCollection 2016 Jan 1.

Authors

Chun-Hao Tsai^{1

2}, Ming-Hui Yang^{1

3}, Amos C Hung¹, Shou-Cheng Wu⁴, Wen-Chin Chiu⁵, Ming-Feng Hou^{6

7}, Yu-Chang Tyan^{1

8

9

10}, Yun-Ming Wang⁴, Shyng-Shiou F Yuan^{1

2

3

11

12

13}

Affiliations

¹ Translational Research Center , Kaohsiung Medical University Hospital , Kaohsiung Medical University , Kaohsiung , Taiwan.
² Graduate Institute of Medicine , College of Medicine , Kaohsiung Medical University , Kaohsiung , Taiwan . Email: yuanssf@ms33.hinet.net ; Tel: +886-7-3121101 Ext2557.
³ Department of Medical Research , Kaohsiung Medical University Hospital , Kaohsiung Medical University , Kaohsiung , Taiwan.
⁴ Department of Biological Science and Technology and Institute of Molecular Medicine and Bioengineering , National Chiao Tung University , Hsinchu , Taiwan . Email: ymwang@mail.nctu.edu.tw ; Tel: +886-3-5712121 Ext56972.
⁵ Division of Thoracic Surgery , Department of Surgery , Kaohsiung Medical University Hospital , Kaohsiung Medical University , Kaohsiung , Taiwan.
⁶ Cancer Center , Kaohsiung Medical University Hospital , Kaohsiung Medical University , Kaohsiung , Taiwan.
⁷ Department of Surgery , Kaohsiung Municipal Ta-Tung Hospital , Kaohsiung , Taiwan.
⁸ Department of Medical Imaging and Radiological Sciences , Kaohsiung Medical University , Kaohsiung , Taiwan.
⁹ Center for Infectious Disease and Cancer Research , Kaohsiung Medical University , Kaohsiung , Taiwan.
¹⁰ Institute of Medical Science and Technology , National Sun Yat-sen University , Kaohsiung , Taiwan.
¹¹ Department of Obstetrics and Gynecology , Kaohsiung Medical University Hospital , Kaohsiung Medical University , Kaohsiung , Taiwan.
¹² Faculty and College of Medicine , Kaohsiung Medical University , Kaohsiung , Taiwan.
¹³ Center for Lipid and Glycomedicine Research , Kaohsiung Medical University , Kaohsiung , Taiwan.

Abstract

Exposure to arsenic is known to be a risk factor for various types of cancer. Apart from its carcinogenic activity, arsenic also shows promoting effects on angiogenesis, a crucial process for tumor growth. Yet, the mechanism underlying arsenic-induced angiogenesis is not fully understood. In this study, we aimed at investigating the involvement of inhibitor of DNA binding 1 (Id1) and the associated signal molecules in the arsenic-mediated angiogenesis. Our initial screening revealed that treatment with low concentrations of arsenic (0.5-1 μM) led to multiple cellular responses, including enhanced endothelial cell viability and angiogenic activity as well as increased protein expression of Id1. The arsenic-induced angiogenesis was suppressed in the Id1-knocked down cells compared to that in control cells. Furthermore, arsenic-induced Id1 expression and angiogenic activity were regulated by PI3K/Akt, NF-κB, and nitric oxide synthase (NOS) signaling. In summary, our current data demonstrate for the first time that Id1 mediates the arsenic-promoted angiogenesis, and Id1 may be regarded as an antiangiogenesis target for treatment of arsenic-associated cancer.