title: Calphostin C, a remarkable multimodal photodynamic killer of neoplastic cells by selective nuclear lamin B1 destruction and apoptogenesis (Review).
abstract: Perylenequinones that generate reactive oxygen species (ROS) when illuminated with visible light have been recommended as photodynamic chemotherapeutic agents. One of these is calphostin C (CalC), the action of the photo-activated derivative of which, CalCphiE, has been ascribed to its ability to selectively and irreversibly inhibit protein kinase Cs (PKCs). But recent results of experiments with neoplastic rat fibroblasts and human breast and uterine cervix cancer cells have revealed that the action of CalCphiE involves more than PKC inhibition. Besides suppressing PKC activity, CalCphiE rapidly causes endoplasmic reticulum (ER) stress in breast cancer cells and the selective complete oxidation and proteasomal destruction of the functionally essential nuclear envelope protein lamin B1, in human cervical carcinoma (HCC) cells and neoplastic rat fibroblasts. When these lamin B1-lacking cells are placed in the dark, cytoplasmic membrane-linked PKC activities suddenly rebound and apoptogenesis is initiated as indicated by the immediate release of cytochrome c from mitochondria and later on the activation of caspases. Hence, CalCphiE is a photodynamic cytocidal agent attacking multiple targets in cancer cells and it would be worth determining, even for their best applicative use, whether other perylenequinones also share the so far unexpectedly complex deadly properties of the CalCphiE.
authors.affiliation: Department of Biomedical and Surgical Sciences, University of Verona Medical School, I-37134 Verona, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Chiarini
authors.forename: James F
authors.initials: JF
authors.lastname: Whitfield
authors.forename: Raffaella
authors.initials: R
authors.lastname: Pacchiana
authors.forename: Maddalena
authors.initials: M
authors.lastname: Marconi
authors.forename: Ubaldo
authors.initials: U
authors.lastname: Armato
authors.forename: Ilaria
authors.initials: I
authors.lastname: Dal Prà
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002467:Cell Nucleus / Q000187:drug effects; D006801:Humans; D034921:Lamin Type B / Q000187:drug effects*; D009281:Naphthalenes / Q000494:pharmacology*; D010778:Photochemotherapy / Q000379:methods
chemical_list: D000903:Antibiotics, Antineoplastic; D034921:Lamin Type B; D009281:Naphthalenes; C058819:calphostin C