Nucleoplasmic calcium buffering sensitizes human squamous cell carcinoma to anticancer therapy

Lídia M. Andrade, Jony M. Geraldo, Osvaldo X. Gonçalves, Miguel T.T. Leite, Anderson M. Catarina, Melissa M. Guimarães, Adriana F.P. Leme, Sami Yokoo, Carlos R. Machado, Matheus A. Rajão, Sandhra M. Carvalho, Dawidson A. Gomes, Carla J. Aguiar, Elaine M. Souza-Fagundes, Carlos L. Zani, Rodrigo R. Resende, Olindo A. Martins-Filho, M. Fátima Leite

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15 Citas (Scopus)

Resumen

Background: Calcium (Ca 2+) signaling within the nucleus is known to play a crucial role in cell proliferation. The aim of this study was to investigate whether nuclear Ca 2+ buffering could improve the antitumor effect of X-rays therapy on Human Squamous Cell Carcinoma (HSCC). Methods: For these purpose, we developed an experimental protocol that simulated clinical radiotherapy and prevented bystander effects of irradiation. HSCC, A431 cell line, was submitted to 10Gy cumulative X-rays therapy alone (XR Cd10Gy) or in association with the strategy that selectively buffer nuclear Ca 2+ (Ca 2+n) signaling. Results: Upon Ca 2+n buffering, A431 cell proliferation rate decreased significantly as compared to control. Cell cycle analysis showed that association of Ca 2+n buffering with XR Cd 10Gy increased the percentage of A431 cells at G 2/M and did not increase nuclear/mitochondrial DNA damages. Nonetheless, Ca 2+n buffering prevented the increase of the radioresistance-related biomarker ADAM-17 expression and EGFR activation induced by irradiation. Furthermore, the association therapy almost completely abolished cell survival fraction even using approximately half of the X-rays cumulative dose. Conclusions: Nuclear Ca 2+ buffering sensitizes human squamous cell carcinoma to X-rays irradiation treatment.

Idioma originalInglés
Páginas (desde-hasta)131-139
Número de páginas9
PublicaciónJournal of Cancer Science and Therapy
Volumen4
N.º5
DOI
EstadoPublicada - 2012
Publicado de forma externa

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