title: Autophagy inhibition sensitizes bladder cancer cells to the photodynamic effects of the novel photosensitizer chlorophyllin e4.
abstract: We previously developed a novel photosensitizer, chlorophyllin e4, and found that chlorophyllin e4 mediated-PDT could kill 5637 and T24 cells by inducing apoptotic cell death. Here, we further investigated the new mechanism of autophagy and determined its relevance to apoptosis in e4-PDT. We demonstrated that chlorophyllin e4 was located in both lysosome and mitochondria, and autophagy also occurred in bladder cancer cells upon e4-PDT. More importantly, autophagy played a pro-survival role, and its inhibition enhanced e4-PDT-associated apoptotic cell death because cells pretreated with the typical autophagy inhibitor either 3-methyladenine or Bafilomycin A1 exhibited much lower cell viability and higher apoptotic cell death. Thus, these data imply that the combination of PDT, when mediated by our new photosensitizer chlorophyllin e4, and an autophagy inhibitor might be a promising approach to the eliminationof non-muscle invasive bladder cancer.
authors.affiliation: Department of Urology, Jin Shan Hospital, Fudan University, Shanghai, China.
authors.forename: Lihuan
authors.initials: L
authors.lastname: Du
authors.affiliation: Department of Urology, Gongli Hospital, Shanghai, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Jiang
authors.affiliation: Department of Urology, Gongli Hospital, Shanghai, China.
authors.forename: Guozeng
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Immunology, Fudan University, Shanghai, China.
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Chu
authors.affiliation: Department of Immunology, Fudan University, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lin
authors.affiliation: Department of Immunology, Fudan University, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Qian
authors.affiliation: Department of Urology, Hua Shan Hospital, Fudan University, Shanghai, China.
authors.forename: Yuanfang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Urology, Gongli Hospital, Shanghai, China.
authors.forename: Jingcun
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Urology, Jin Shan Hospital, Fudan University, Shanghai, China. Electronic address: 13918043956@163.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002735:Chlorophyllides / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008247:Lysosomes / Q000737:chemistry / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology
chemical_list: D002735:Chlorophyllides; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D017319:Photosensitizing Agents; C025946:3-methyladenine; C007020:chlorophyllin; D000225:Adenine
keywords: Apoptosis; Autophagy; Bladder cancer; Chlorophyllin e4; Photodynamic