Bradykinin-induced Ca2+ signaling in human oral squamous cell carcinoma HSC-3 cells

Abstract

Cytosolic Ca 2+ is an important regulator of tumor cell proliferation and metastasis. Recently, the strategy of blocking receptors and channels specific to certain cancer cell types has emerged as a potentially viable future treatment. Oral squamous cell carcinoma is an aggressive form of cancer with a high metastasis rate but the receptormechanisms involved in Ca 2+ signaling in these tumors have not yet been elucidated. In our present study, we report that bradykinin induces Ca 2+ signaling and its modulation in the human oral squamous carcinoma cell line, HSC-3. Bradykinin was found to increase the cytosolic Ca 2+ levels in a concentration-dependent manner. This increase was inhibited by pretreatment with the phospholipase C-β inhibitor, U73122, and also by 2-aminoethoxydiphenyl borate, an inhibitor of the inositol 1,4,5-trisphosphate receptor. Pretreatment with extracellular ATP also inhibited the peak bradykinin-induced Ca 2+ rise. In contrast, the ATP-induced rise in cytosolic Ca 2+ was not affected by pretreatment with bradykinin. Pretreatment of the cells with either forskolin or phorbol 12-myristate 13-acetate (activators of adenylyl cyclase and protein kinase C, respectively) prior to bradykinin application accelerated the recovery of cytosolic Ca 2+ to baseline levels. These data suggest that bradykinin receptors are functional in Ca 2+ signaling in HSC-3 cells and may therefore represent a future target in treatment strategies for human oral squamous cell carcinoma.