n-caproylsphingosine and Salivary-Gland-Neoplasms

C6-ceramide is an exogenous short-chain ceramide which can induce apoptosis of multiple cancer cells. Salivary adenoid cystic carcinoma (SACC) is a common salivary gland cancer, which possesses of high rate of local recurrence and distant metastasis. The mechanism of ceramide-induced SACC-83 and SACC-LM cell apoptosis has not been revealed. In our study, gene expression microarray was used to discover that the unfolded protein response (UPR) pathway, especially PRKR-like endoplasmic reticulum kinase (PERK) pathway, was the major activated pathway after treatment of c6-ceramide. D1ER, an endoplasmic-reticulum-targeted Ca2+ indicator, was used to measure Ca2+ release from endoplasmic reticulum (ER) dynamically. We found that inositol 1,4,5-trisphosphate receptor 3 (IP3R3) was activated, leading to Ca2+ release from ER, soon after c6-ceramide treatment. IP3R3 silencing could block UPR, although it could not prevent SACC-83 and SACC-LM cells from apoptosis. Moreover, we found that C/EBP-homologous protein could upregulate in a UPR-independent way. Mitochondria outer membrane permeabilization might play an important role in inducing SACC cell apoptosis.

Topics: Animals; Apoptosis; Calcium; Carcinoma, Adenoid Cystic; Cell Line, Tumor; Cell Proliferation; Ceramides; Cytosol; eIF-2 Kinase; Endoplasmic Reticulum; Gene Expression Regulation, Neoplastic; Gene Silencing; Humans; Inositol 1,4,5-Trisphosphate Receptors; Ki-67 Antigen; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Mitochondrial Membranes; Oligonucleotide Array Sequence Analysis; Salivary Gland Neoplasms; Signal Transduction; Unfolded Protein Response; Xenograft Model Antitumor Assays