Overexpression of the human inducible nitric oxide synthase gene enhances radiation-induced apoptosis in colorectal cancer cells via a caspase-dependent mechanism.
Nitric oxide (NO) has been reported to sensitize cancer cells to radiation. Since delivery of NO to tumors is limited in vivo by systemic toxicity of NO, we examined the potential of gene delivery of the human inducible nitric oxide synthase (iNOS) gene as a means of achieving high output NO production. We successfully transduced two colorectal cancer cell lines as evidenced by increased iNOS protein accumulation and nitrite production. We found that overexpression of iNOS enhanced the effects of radiation on apoptosis in both cell lines in a caspase-dependent fashion. Gene transfer of iNOS holds much promise as a potential radiosensitizer of cancer cells since it increases apoptosis in an additive manner with radiation.
Chung
Peter
P
Department of Surgery, University of Pittsburgh School of Medicine, Cancer Pavillion, 5150 Centre Avenue, Rm 438, Pittsburgh, PA 15232, USA.
Cook
Tracy
T
Liu
Kaihong
K
Vodovotz
Yoram
Y
Zamora
Ruben
R
Finkelstein
Sydney
S
Billiar
Timothy
T
Blumberg
David
D
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor / Q000187:drug effects* / Q000528:radiation effects; D015179:Colorectal Neoplasms / Q000628:therapy; D003131:Combined Modality Therapy; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D007763:Lac Operon; D020030:Nitric Oxide Donors; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics* / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine; D013997:Time Factors; D014161:Transduction, Genetic
D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D020030:Nitric Oxide Donors; D011838:Radiation-Sensitizing Agents; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D026423:S-Nitroso-N-Acetylpenicillamine; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D020169:Caspases