Involvement of both endoplasmic reticulum and mitochondria in photokilling of nasopharyngeal carcinoma cells by the photosensitizer Zn-BC-AM

Nai Ki MAK, Kai Man Li, Wing Nang Leung, Ricky N S WONG, Dolly P. Huang, Maria Li Lung, Yan Kin Lau, Chi K. Chang

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)

Abstract

Photodynamic therapy (PDT) is recently developed as an effective treatment for malignant disease. In PDT, the photosensitizer eradicates tumour by induction of apoptosis. In this study, we investigated the mechanistic actions of a recently developed second generation photosensitizer, Zn-BC-AM, on nasopharyngeal carcinoma (NPC) cells. Zn-BC-AM was found to localize in the mitochondria, endoplasmic reticulum (ER), and golgi body. Photoactivation of Zn-BC-AM loaded NPC cells resulted in a rapid collapse of mitochondrial membrane potential (Δψ m) (15 min), followed by the release of cytochrome c (1 h), and activation of caspases-9 and -3 (4 h). Expression of ER chaperones Bip/Grp78 and Grp94, and ER resident lectin-like chaperone calnexin (CNX) was also enhanced in PDT-stressed NPC cells. Caspase-12, an important caspase involved in ER stress-induced apoptosis, was also activated. Inhibition of Ca 2+ uptake into mitochondria by ruthenium red (RR) or loading the cells with EGTA-AM, an agent that buffers intracellular Ca 2+ released from ER, resulted in a significant reduction of Zn-BC-AM PDT-induced cell death. These observations suggest that both ER and mitochondria are the subcellular targets of Zn-BC-AM. Effective activation of ER- and mitochondria-mediated apoptotic pathways is responsible for Zn-BC-AM PDT-induced NPC cell death.

Original languageEnglish
Pages (from-to)2387-2396
Number of pages10
JournalBiochemical Pharmacology
Volume68
Issue number12
DOIs
Publication statusPublished - 15 Dec 2004

Scopus Subject Areas

  • Biochemistry
  • Pharmacology

User-Defined Keywords

  • Caspase-12
  • ER-stress
  • Mitochondrial membrane potential
  • Nasopharyngeal carcinoma
  • Photodynamic therapy

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