title: Lamin A/C cleavage by caspase-6 activation is crucial for apoptotic induction by photodynamic therapy with hexaminolevulinate in human B-cell lymphoma cells.
abstract: Photodynamic therapy (PDT) with a light-activated drug is an approved modality for cancer treatment. Hexaminolevulinate (HAL), a hexylester of 5-aminolevulinic acid as the photosensitising protoporphyrin IX (PpIX) precursor, is clinically used for both PDT and photodetection. Our previous studies have shown that HAL-PDT can effectively induce apoptosis in several human blood malignant cell lines. However, the mechanisms involved in the apoptotic induction are still not fully elucidated. In this study we have focused on the role of cellular lamin A/C in the apoptotic induction. HAL-PDT-mediated apoptosis was confirmed by various techniques including fluorescence microscopy and electron microscopy in both human B-cell lymphoma Ramos and Daudi cell lines. The lamin A/C, together with caspases-6 and -3, was cleaved during the apoptosis. Western blots, immunocytochemistry, fluorescence microscopy and electron microscopy demonstrated that the specific caspase-6 inhibitor abrogated the HAL-PDT-mediated cleavages of both caspase-6 and lamin A/C and subsequent apoptosis in these two cell lines, suggesting that the cleavage of lamin A/C by the caspase-6 activation is crucial for such apoptotic induction.
authors.affiliation: Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital and Medical Faculty, University of Oslo, Oslo, Norway.
authors.forename: Susan
authors.initials: S
authors.lastname: Shahzidi
authors.forename: Andreas
authors.initials: A
authors.lastname: Brech
authors.forename: Mouldy
authors.initials: M
authors.lastname: Sioud
authors.forename: Xiaoran
authors.initials: X
authors.lastname: Li
authors.forename: Zhenhe
authors.initials: Z
authors.lastname: Suo
authors.forename: Jahn M
authors.initials: JM
authors.lastname: Nesland
authors.forename: Qian
authors.initials: Q
authors.lastname: Peng
mesh_terms: D000622:Aminolevulinic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D053178:Caspase 6 / Q000378:metabolism*; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D006801:Humans; D034904:Lamin Type A / Q000235:genetics / Q000378:metabolism*; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D010778:Photochemotherapy; D059748:Proteolysis
chemical_list: D034904:Lamin Type A; C440308:lamin C; D000622:Aminolevulinic Acid; D053178:Caspase 6
keywords: 5-aminolevulinic acid; ALA; Apoptosis; Caspase-6; HAL; Hexaminolevulinate; Lamin A/C; Lymphoma; PDT; Photodynamic therapy; PpIX; TdT; hexaminolevulinate; photodynamic therapy; protoporphyrin IX; terminal deoxynucleotid transferase