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

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)131-139
Number of pages9
JournalJournal of Cancer Science and Therapy
Volume4
Issue number5
DOIs
StatePublished - 2012
Externally publishedYes

Keywords

  • A431 cells
  • Head and neck tumor
  • Human squamous cell carcinoma
  • Nuclear calcium buffering
  • X-rays irradiation

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