C6-ceramide induces salivary adenoid cystic carcinoma cell apoptosis via IP3R-activated UPR and UPR-independent pathways

  • Biochem Biophys Res Commun. 2020 May 14;525(4):997-1003. doi: 10.1016/j.bbrc.2020.02.164.
Ling Qiu  1 ,  Zhe Liu  2 ,  Chenzhou Wu  3 ,  Wen Chen  4 ,  Yafei Chen  5 ,  Bowen Zhang  6 ,  Jinjin Li  7 ,  Huabing Liu  8 ,  Nengwen Huang  9 ,  Zhou Jiang  10 ,  Yongzhi Wu  11 ,  Longjiang Li  12
Affiliations
  • 1. Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, No. 14, Section Three, Ren Min Nan Road, Chengdu, Sichuan, 610041, China; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, Section Three, Ren Min Nan Road, Chengdu, Sichuan, 610041, China. Electronic address: [email protected].
  • 2. Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, No. 14, Section Three, Ren Min Nan Road, Chengdu, Sichuan, 610041, China; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, Section Three, Ren Min Nan Road, Chengdu, Sichuan, 610041, China. Electronic address: [email protected].
  • 3. Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, No. 14, Section Three, Ren Min Nan Road, Chengdu, Sichuan, 610041, China; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, Section Three, Ren Min Nan Road, Chengdu, Sichuan, 610041, China. Electronic address: [email protected].
  • 4. Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, No. 14, Section Three, Ren Min Nan Road, Chengdu, Sichuan, 610041, China; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, Section Three, Ren Min Nan Road, Chengdu, Sichuan, 610041, China. Electronic address: [email protected].
  • 5. Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, No. 14, Section Three, Ren Min Nan Road, Chengdu, Sichuan, 610041, China; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, Section Three, Ren Min Nan Road, Chengdu, Sichuan, 610041, China. Electronic address: [email protected].
  • 6. Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, No. 14, Section Three, Ren Min Nan Road, Chengdu, Sichuan, 610041, China; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, Section Three, Ren Min Nan Road, Chengdu, Sichuan, 610041, China. Electronic address: [email protected].
  • 7. Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, No. 14, Section Three, Ren Min Nan Road, Chengdu, Sichuan, 610041, China; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, Section Three, Ren Min Nan Road, Chengdu, Sichuan, 610041, China. Electronic address: [email protected].
  • 8. Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, No. 14, Section Three, Ren Min Nan Road, Chengdu, Sichuan, 610041, China; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, Section Three, Ren Min Nan Road, Chengdu, Sichuan, 610041, China. Electronic address: [email protected].
  • 9. Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, No. 14, Section Three, Ren Min Nan Road, Chengdu, Sichuan, 610041, China; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, Section Three, Ren Min Nan Road, Chengdu, Sichuan, 610041, China. Electronic address: [email protected].
  • 10. Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, No. 14, Section Three, Ren Min Nan Road, Chengdu, Sichuan, 610041, China; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, Section Three, Ren Min Nan Road, Chengdu, Sichuan, 610041, China. Electronic address: [email protected].
  • 11. Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, No. 14, Section Three, Ren Min Nan Road, Chengdu, Sichuan, 610041, China; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, Section Three, Ren Min Nan Road, Chengdu, Sichuan, 610041, China. Electronic address: [email protected].
  • 12. Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, No. 14, Section Three, Ren Min Nan Road, Chengdu, Sichuan, 610041, China; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, Section Three, Ren Min Nan Road, Chengdu, Sichuan, 610041, China. Electronic address: [email protected].
PMID: 32178876 DOI: 10.1016/j.bbrc.2020.02.164
Abstract

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.

Keywords
Apoptosis; Ceramide; Inositol 1,4,5-trisphosphate receptor; Mitochondria outer membrane permeabilization; Unfolded protein response.
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