Doxorubicin inhibits the production of nitric oxide by colorectal cancer cells.
Doxorubicin (DOX) is an active and broad spectrum chemotherapeutic agent. Increased inducible nitric oxide synthase (NOS) expression and/or activity have been reported in several human tumors. While the relationship between DOX treatment and the enzymatic activity of endothelial NOS has been well characterized, little is known about the effects of DOX on the expression of iNOS in human cancer cells. In the present study, we characterized the effects of DOX on the nitric oxide (NO) production by colorectal cancer cells, DLD-1. IFN-gamma/IL-1beta (CM) increased the production of NO, whereas pretreatment of DOX inhibited the production of NO in response to CM in a dose dependent manner. The increased expressions of iNOS mRNA and protein by CM were completely blocked by DOX without affecting the iNOS mRNA stability. However, DOX activated nuclear factor-kappaB (NF-kappaB) in response to CM. Furthermore, the expression of inhibitor kappaB alpha was reduced by DOX in a dose dependent manner. Collectively, DOX inhibited the production of NO by DLD-1 cells, which is not linked to well known transcription factor, NF-kappaB. Therefore, further studies on the possible mechanisms of inhibitory effects of NO production by DOX would be worth pursuing.
Jung
In Duk
ID
College of Medicine, Konyang University, Nonsan, Korea.
Lee
Jang-Soon
JS
Yun
Seong Young
SY
Park
Chang Gyo
CG
Han
Jeung Whan
JW
Lee
Hyang Woo
HW
Lee
Hoi Young
HY
D015179:Colorectal Neoplasms / Q000378:metabolism*; D004317:Doxorubicin / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D004317:Doxorubicin; D019001:Nitric Oxide Synthase