Sulfasalazine induces apoptosis of HBx-expressing cells in an NF-kappaB-independent manner.
The Hepatitis B virus (HBV) is a causative agent of acute chronic hepatitis, cirrhosis, and hepatocarcinoma. The Hepatitis B virus X protein (HBx) has pleiotypic functions in the regulation of proliferation and apoptosis. It has been suggested that the anti-inflammatory drug sulfasalazine, which is commonly used to treat rheumatoid arthritis and inflammatory bowel disease, inhibits nuclear factor NF-kappaB and induces cell death in HBx-expressing liver cells. In this study, we demonstrate that sulfasalazine induces cell death via apoptosis in HBx-expressing liver cells, as evidenced by characteristic changes in nuclear morphology, cleavage of poly (ADP-ribose) polymerase (PARP), caspase-3 and caspase-9, and activation of caspase-3. We also demonstrate that inhibition of NF-kappaB by siRNA fails to induce apoptosis of HBx-expressing liver cells, indicating that sulfasalazine modulates apoptosis of HBx-expressing cells in an NF-kappaB-independent manner.
Lee
Young-Man
YM
Indang Institute of Molecular Biology, Inje University, Jeodong 2-Ga 64, Chung-Ku, Seoul, 100-032, Republic of Korea.
Kang
Moonkyung
M
Hwang
Jung-Me
JM
Lee
Sukyung
S
Cho
Hyeseong
H
Kim
Yeon-Soo
YS
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D006515:Hepatitis B virus / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D012460:Sulfasalazine / Q000494:pharmacology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins
D016328:NF-kappa B; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D012460:Sulfasalazine; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D053453:Caspase 9