TY - JOUR
T1 - Nucleoplasmic calcium buffering sensitizes human squamous cell carcinoma to anticancer therapy
AU - Andrade, Lídia M.
AU - Geraldo, Jony M.
AU - Gonçalves, Osvaldo X.
AU - Leite, Miguel T.T.
AU - Catarina, Anderson M.
AU - Guimarães, Melissa M.
AU - Leme, Adriana F.P.
AU - Yokoo, Sami
AU - Machado, Carlos R.
AU - Rajão, Matheus A.
AU - Carvalho, Sandhra M.
AU - Gomes, Dawidson A.
AU - Aguiar, Carla J.
AU - Souza-Fagundes, Elaine M.
AU - Zani, Carlos L.
AU - Resende, Rodrigo R.
AU - Martins-Filho, Olindo A.
AU - Leite, M. Fátima
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - A431 cells
KW - Head and neck tumor
KW - Human squamous cell carcinoma
KW - Nuclear calcium buffering
KW - X-rays irradiation
UR - http://www.scopus.com/inward/record.url?scp=84863227112&partnerID=8YFLogxK
U2 - 10.4172/1948-5956.1000127
DO - 10.4172/1948-5956.1000127
M3 - Artículo Científico
AN - SCOPUS:84863227112
SN - 1948-5956
VL - 4
SP - 131
EP - 139
JO - Journal of Cancer Science and Therapy
JF - Journal of Cancer Science and Therapy
IS - 5
ER -
