Lamin B1, a major component of the nuclear lamina, anchors the nucleus to the cytoskeletal cage, and controls nuclear orientation, chromosome positioning and, alongside several
enzymes, fundamental nuclear functions. Exposing polyomavirus-transformed rat pyF111 fibroblasts and human cervical
carcinoma (HCC) C4-I cells for 30 min to photoexcited
perylenequinone calphostin C, i.e. Cal C(phiE), an established
reactive oxygen species (ROS)-generator and
protein kinase C (PKC) inhibitor, caused the cells to selectively oxidize and then totally destroy their nuclear
lamin B1 by only 60 min after starting the treatment, i.e. when apoptotic
caspases' activities had not yet increased. However, while the oxidized
lamin B1 was being destroyed,
lamins A/C, the
lamin A-associated nuclear envelope
protein emerin, and the nucleoplasmic
protein cyclin E were neither oxidized nor destroyed. The oxidized
lamin B was ubiquitinated and demolished in the
proteasome probably by an enhanced
peptidyl-glutaminase-like activity. Hence, the Cal C(phiE)-induced rapid and selective
lamin B1 oxidation and proteasomal destruction ahead of the activation of apoptotic
caspases was by itself a most severe molecular lesion impairing vital nuclear functions. Conversely, Cal C directly added to the cells kept in the dark damaged neither nuclear
lamin B1 nor cell viability. Thus, our findings reveal a novel cell-damaging mechanism of a photodynamic
tumor therapeutic agent.