title: Photoactivation of 9-hydroxypheophorbide alpha triggers apoptosis through the reactive oxygen species-mediated mitochondrial pathway and endoplasmic reticulum stress in AMC-HN-3 laryngeal cancer cells.
abstract: Photodynamic therapy (PDT) is a promising treatment modality for a variety of cancers. It utilizes light-absorbing compounds combined with direct illumination to generate reactive oxygen species in photosensitizer-targeted tumor cells resulting in the final photodamage of tumors. Recently, we demonstrated that a combination modality of 9-hydroxypheophorbide alpha (9-HPbD)-based PDT and carboplatin exerts enhanced cytotoxic and apoptotic effects on AMC-HN-3 laryngeal cancer cells. The present study aimed to investigate the potential apoptotic pathways initiated by 9-HPbD-PDT-mediated reactive oxygen species (ROS) in AMC-HN-3 cells. Cytotoxicity and apoptosis induced by 9-HPbD-PDT were exhibited in a ROS-dependent manner. Mitochondria and the endoplasmic reticulum (ER) were observed as preferential sites of 9-HPbD accumulation in AMC-HN-3 cells. ROS induced by 9-HPbD-PDT directly led to downregulated expression of Bcl-2, loss of mitochondrial membrane potential, release of cytochrome c from mitochondria, elevation of intracellular calcium due to ER stress, as well as induction of CHOP and activation of caspase-3, -8, -9 and -12. Our results demonstrated that ROS induced by 9-HPbD-PDT play a causative role in triggering mitochondrial events, ER stress and probable involvement of the extrinsic apoptotic pathway in AMC-HN-3 cells.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Dankook University, Cheonan 330-715, Republic of Korea.
authors.forename: Peijie
authors.initials: P
authors.lastname: He
authors.forename: Jin-Chul
authors.initials: JC
authors.lastname: Ahn
authors.forename: Jang-In
authors.initials: JI
authors.lastname: Shin
authors.forename: Phil-Sang
authors.initials: PS
authors.lastname: Chung
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D016190:Carboplatin / Q000494:pharmacology; D045744:Cell Line, Tumor; D002734:Chlorophyll / Q000031:analogs & derivatives* / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007822:Laryngeal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D017319:Photosensitizing Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013997:Time Factors
chemical_list: C491791:9-hydroxypheophorbide alpha; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; D002734:Chlorophyll; D045304:Cytochromes c; D016190:Carboplatin; D002118:Calcium