Oncotarget

Research Papers:

Curcumin induces G2/M cell cycle arrest and apoptosis of head and neck squamous cell carcinoma in vitro and in vivo through ATM/Chk2/p53-dependent pathway

An Hu, Jing-Juan Huang _, Jing-Fei Zhang, Wei-Jun Dai, Rui-Lin Li, Zhao-Yang Lu, Jun-Li Duan, Ji-Ping Li, Xiao-Ping Chen, Jing-Ping Fan, Wei-Hua Xu and Hong-Liang Zheng

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Oncotarget. 2017; 8:50747-50760. https://doi.org/10.18632/oncotarget.17096

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Abstract

An Hu1, Jing-Juan Huang2, Jing-Fei Zhang1, Wei-Jun Dai1, Rui-Lin Li3, Zhao-Yang Lu3, Jun-Li Duan3, Ji-Ping Li4, Xiao-Ping Chen1, Jing-Ping Fan1,5, Wei-Hua Xu1 and Hong-Liang Zheng6

1Department of Otolaryngology, Gongli Hospital, Second Military Medical University, Pudong New Area, Shanghai, 200135, China

2Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, 200030, China

3Department of Gerontology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China

4Department of Otolaryngology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Pudong New Area, Shanghai, 200127, China

5Department of Otolaryngology-Head and Neck Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China

6Department of Otolaryngology-Head and Neck Surgery, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China

Correspondence to:

Jing-Juan Huang, email: hjjxinhua@163.com

Keywords: cell cycle arrest, apoptosis, ATM/Chk2/p53 signal pathway, head and neck squamous cell carcinoma, curcumin

Received: March 20, 2016     Accepted: March 31, 2017     Published: April 13, 2017

ABSTRACT

Studies have demonstrated that curcumin (CUR) exerts its tumor suppressor function in a variety of human cancers including head and neck squamous cell carcinoma (HNSCC). However, the exact underlying molecular mechanisms remain obscure. Here, we aim to test whether CUR affects ATM/Chk2/p53 signaling pathway, leading to the induction of cell cycle arrest, inhibition of angiogenesis of HNSCC in vitro and in vivo. To this end, we conducted multiple methods such as MTT assay, Invasion assay, Flow cytometry, Western blotting, RT-PCR, and transfection to explore the functions and molecular insights of CUR in HNSCC. We observed that CUR significantly induced apoptosis and cell cycle arrest, inhibited angiogenesis in HNSCC. Mechanistically, we demonstrated that CUR markedly up-regulated ATM expression and subsequently down-regulated HIF-1α expression. Blockage of ATM production totally reversed CUR induced cell cycle arrest as well as anti-angiogenesis in HNSCC. Moreover, our results demonstrated that CUR exerts its antitumor activity through targeting ATM/Chk2/p53 signal pathway. In addition, the results of xenograft experiments in mice were highly consistent with in vitro studies. Collectively, our findings suggest that targeting ATM/Chk2/p53 signal pathway by CUR could be a promising therapeutic approach for HNSCC prevention and therapy.


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