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 1 , Jing-Juan Huang 2 , Jing-Fei Zhang 1 , Wei-Jun Dai 1 , Rui-Lin Li 3 , Zhao-Yang Lu 3 , Jun-Li Duan 3 , Ji-Ping Li 4 , Xiao-Ping Chen 1 , Jing-Ping Fan 1, 5 , Wei-Hua Xu 1 and Hong-Liang Zheng 6 1 Department of Otolaryngology, Gongli Hospital, Second Military Medical University, Pudong New Area, Shanghai, 200135, China 2 Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, 200030, China 3 Department of Gerontology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China 4 Department of Otolaryngology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Pudong New Area, Shanghai, 200127, China 5 Department of Otolaryngology-Head and Neck Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China 6 Department 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.