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Article Publish Status: FREE
Abstract Title:

Deguelin Potentiates Apoptotic Activity of an EGFR Tyrosine Kinase Inhibitor (AG1478) in PIK3CA-Mutated Head and Neck Squamous Cell Carcinoma.

Abstract Source:

Int J Mol Sci. 2017 Jan 26 ;18(2). Epub 2017 Jan 26. PMID: 28134774

Abstract Author(s):

Yuh Baba, Toyonobu Maeda, Atsuko Suzuki, Satoshi Takada, Masato Fujii, Yasumasa Kato

Article Affiliation:

Yuh Baba

Abstract:

Head and neck squamous cell carcinoma (HNSCC) is known to be intrinsically resistant to inhibitors for epidermal growth factor receptor (EGFR). Until now, clinical outcomes for HNSCC using EGFR inhibitors as single agents have yielded disappointing results. Here, we aimed to study whether combinatorial treatment using AG1478 (EGFR tyrosine kinase inhibitor) and deguelin, which is a rotenoid isolated from the African plant, could enhance the anti-tumor effects of AG1478 in HNSCC. For Ca9-22 cells with,, andwild types, AG1478 alone suppressed both phosphorylated levels of ERK and AKT and induced apoptosis. On the contrary, for HSC-4 cells withandwild types, and amutant, AG1478 alone did not suppress the phosphorylated level of AKT nor induce apoptosis, while it suppressed ERK phosphorylation. Forced expression of constitutively active(G1633A mutation) significantly reduced the apoptotic effect of AG1478 on thewild-type Ca9-22 cells. When HSC-4 cells with theG1633A mutation were treated with a combination of AG1478 and deguelin, combination effects on apoptosis induction were observed through the inhibition of the AKT pathway. These results suggest that the combination of EGFR tyrosine kinase inhibitor with deguelin is a potential therapeutic approach to treat-mutated HNSCC.

Study Type : In Vitro Study

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