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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.


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-1? 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.

SUBMITTER: Hu A 

PROVIDER: S-EPMC5584201 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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

Hu An A   Huang Jing-Juan JJ   Zhang Jing-Fei JF   Dai Wei-Jun WJ   Li Rui-Lin RL   Lu Zhao-Yang ZY   Duan Jun-Li JL   Li Ji-Ping JP   Chen Xiao-Ping XP   Fan Jing-Ping JP   Xu Wei-Hua WH   Zheng Hong-Liang HL  

Oncotarget 20170413 31


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 <i>in vitro</i> and <i>in vivo</i>. To this end, we conducted multiple methods such as MTT assay, Invasion  ...[more]

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