Cytotoxicity and genotoxicity effects of arsenic trioxide on SQ20B human laryngeal carcinoma cells

Trabelsi, Fatma; Khlifi, Rim; Goux, Didier; Guillamin, Marilyne; Hamza-Chaffai, Amel; Sichel, François

doi:10.1016/j.etp.2017.02.003

Cited by 1 publication

(2 citation statements)

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“…It has been reported that ATO inhibits cell proliferation and migration in the micromolar range (2-5 μM) in HNSCC, and the inhibitory effects of ATO are mainly associated with DNA damage and cell cycle arrest at G2/M (Boyko-Fabian et al, 2014;Trabelsi et al, 2017), but the exact molecular mechanism by which low-dose ATO regulates antimetastatic effects is unclear. Our results presented here, for the first time, clearly demonstrated that ATO dysregulated the CLIP170 zinc finger and inhibited the motility of HNSCC cells at low concentrations.…”

Section: Discussionmentioning

confidence: 99%

“…At the currently approved therapeutic dose (0.15 mg/kg), ATO can cause toxic side-effects to patients (Soignet et al, 2001). Moreover, it has been demonstrated that ATO induces a dose-dependent induction of DNA damages and G2/M arrest in cell cycle in human laryngeal carcinoma SQ20B cell line (Trabelsi et al, 2017), suggesting that ATO, at relatively high concentrations, may exert its anti-cancer effects through cell killing or inducing apoptosis. However, it is unclear whether low-dose, non-cytotoxic ATO (1 μM or lower) is able to suppress HNSCC metastasis.…”

Section: Introductionmentioning

confidence: 99%

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Arsenic trioxide disturbs the LIS1/NDEL1/dynein microtubule dynamic complex by disrupting the CLIP170 zinc finger in head and neck cancer

Xue

Liu

2020

Toxicology and Applied Pharmacology

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Cancer mortality is mainly caused by metastasis, which requires dynamic remodeling of cytoskeletal components such as microtubules. Targeting microtubules presents a promising antimetastatic strategy that could prevent cancer spreading and recurrence. It is known that arsenic trioxide (ATO) is able to inhibit the migration and invasion of solid malignant tumors, but its exact molecular mechanism remains unclear. Here, we report a novel molecular target and antimetastatic mechanism of ATO in head and neck squamous cell carcinoma (HNSCC). We found that cytoplasmic linker protein 170 (CLIP170) was overexpressed in HNSCC tissues and cells compared to normal controls. ATO at non-cytotoxic level (1 μM) inhibited the migration and invasion of HNSCC cells by displacing zinc in the zinc finger motif of CLIP170, which is a key protein that controls microtubule dynamics. The antimetastatic effects of ATO were equivalent to those of siRNA-mediated CLIP170 knockdown. Furthermore, ATO dysregulated microtubule polymerization via the CLIP170/LIS1/NDEL1/dynein signaling pathway in Cal27 cells as a functional consequence of CLIP170 zinc finger disruption. The effect was partially reversed by zinc supplementation. Taken together, these findings reveal that CLIP170 is a novel molecular

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%