2. Academic Validation
  3. C6-ceramide induces salivary adenoid cystic carcinoma cell apoptosis via IP3R-activated UPR and UPR-independent pathways

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

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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