Ionizing radiation and nitric oxide donor sensitize Fas-induced apoptosis via up-regulation of Fas in human cervical cancer cells.
Fas/CD95/Apo1 is a transmembrane receptor known to trigger apoptotic cell death in several cell types. In the present study, we showed that ionizing radiation (IR) and NO donor, S-nitroso-N-acetyl-penicillamine (SNAP), sensitized Fas-induced apoptotic cell death of HeLa human cervical cancers. Suboptimal dose of IR and SNAP up-regulated the cell-surface Fas antigen, detected by FACScan using FITC-anti-Fas antibody. When combined with IR or SNAP, agonistic anti-Fas antibody CH-11 resulted in marked enhancement of apoptosis. This sensitization was completely abrogated by anti-Fas neutralizing antibody ZB4. During the IR and SNAP sensitized Fas-induced apoptosis, mitochondria permeabilization, cytochrome c release, and DNA fragmentation were detected. Furthermore, combined treatment of IR and SNAP additively up-regulated the surface Fas protein expression and sensitized Fas-induced apoptosis. Our findings demonstrate that sensitization of HeLa cervical cells to Fas-mediated apoptosis by IR and NO donor is most likely due to the up-regulation of Fas expression and also provides a means with which to sensitize tumors to the killing effects of cancer therapy via the Fas receptor.
Park
In-Chul
IC
Laboratory of Cell Biology, Korea Cancer Center Hospital, 215-4 Gongneung-Dong, Nowon-Ku, Seoul 139-706, Korea.
Woo
Sang-Hyeok
SH
Park
Myung-Jin
MJ
Lee
Hyung-Chahn
HC
Lee
Su-Jae
SJ
Hong
Young-Joon
YJ
Lee
Seung-Hoon
SH
Hong
Seok-Il
SI
Rhee
Chang-Hun
CH
D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D006367:HeLa Cells / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D011839:Radiation, Ionizing; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation; D019014:fas Receptor / Q000378:metabolism*
D017304:Annexin A5; D020030:Nitric Oxide Donors; D019014:fas Receptor; D026423:S-Nitroso-N-Acetylpenicillamine; D045304:Cytochromes c; D020169:Caspases