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