Curcumin induces G2/M cell cycle arrest and apoptosis of head and neck squamous cell carcinomain vitroandin vivothrough 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-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.

Combination Delivery of Alpha-Tocopheryl Succinate and Curcumin Using a GSH-Sensitive Micelle (PAH-SS-PLGA) to Treat Pancreatic Cancer

“…In this study, the cell cycle analysis was carried out for PAN02 pancreatic cancer cells after treating with free TOS, curcumin, and TOS/curcumin-loaded micelles for 48 h. As shown in Figure 5 b, PAN02 cells treated with free TOS and TOS + free curcumin showed a higher accumulation of cells in the G0G1, while TOS and or curcumin-loaded micelles showed cell inhibition at the G2M phase compared to that of the untreated PAN02 pancreatic cancer cells. A similar observation was observed that showed curcumin-mediated cell cycle arrest at G0G1 and G2M checkpoints [ 43 ].…”

Different p53 genotypes regulating different phosphorylation sites and subcellular location of CDC25C associated with the formation of polyploid giant cancer cells

“…CHK2 is regulated by ATM after DNA double strand breaks and participates in the checkpoint regulation by phosphorylating CDC25C-Ser216. Compared with ATR-CHK1, ATM-CHK2 aims to provide a rapid protective response to DNA damage in cells [23,24].…”

Impact of curcumin on replicative and chronological aging in the Saccharomyces cerevisiae yeast

“…Curcumin has been found to be biologically active against a variety of tumour types. It induces G2/M cell cycle arrest of head and neck squamous cell carcinoma and in colorectal cancer (Hu et al 2017, Jaiswal et al 2002. Curcumin has also been found to inhibit the growth of two pancreatic cancers cell lines in a dose-and time-dependent manner (Zhu and Bu 2017).…”