Download Synthetic bile acid derivatives induce apoptosis through a c

Ácido ursodeoxicólico induz apoptose em células do carcinoma cervical humano via c-Jun-Nterminal kinase e NF-kappab
Synthetic bile acid derivatives induce apoptosis through a cJun N-terminal kinase and NF-kappaB-dependent process in
human cervical carcinoma cells.
Im E1, Choi SH, Suh H, Choi YH, Yoo YH, Kim ND.
Cancer Lett. 2005 Nov 8;229(1):49-57. Epub 2005 Jan 18.
Author information
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1
Department of Pharmacy and Pusan Cancer Research Center, Pusan National
University, Busan 609-735, South Korea.
Abstract
Recently, we have reported that a synthetic derivative of ursodeoxycholic acid (UDCA), HS1183, and those of chenodeoxycholic acid (CDCA), HS-1199 and HS-1200, induced apoptosis
in human breast carcinoma cells through a p53-independent pathway. Here, we present that the
synthetic bile acid derivatives induce apoptosis in SiHa human cervical carcinoma cells as well.
The parental compounds, UDCA and CDCA, exhibited no significant effect on the cell viability at
the concentration ranges tested. However, their synthetic bile acid derivatives significantly
decreased cell viability in a concentration dependent manner. Characteristic manifestations of
apoptosis including DNA fragmentation, an increased level of proapoptotic protein Bax, and
cleavage of poly(ADP-ribose) polymerase were shown when the cells were treated with these
synthetic compounds. Nuclear translocation of nuclear transcription factor NF-kappaB was
increased and this suggests that the synthetic compounds induce apoptosis in a NF-kappaB
dependent pathway. Phosphorylations of p38 and extracellular signal-regulated kinase were not
affected, whereas c-Jun N-terminal kinase (JNK) was activated along with an increased level of
transcription factor c-Jun. Our studies demonstrate that the newly synthesized bile acids are
capable of inhibiting cell proliferation and inducing apoptosis in SiHa cells through activation of
JNK and NF-kappaB.
PMID:
16157218