Synthetic bile acid derivatives induce apoptosis through a c-Jun N-terminal kinase and NF-kappaB-dependent process in human cervical carcinoma cells.
Recently, we have reported that a synthetic derivative of ursodeoxycholic acid (UDCA), HS-1183, 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.
Im
Eunok
E
Department of Pharmacy and Pusan Cancer Research Center, Pusan National University, Busan 609-735, South Korea.
Choi
Sang-Ho
SH
Suh
Hongsuk
H
Choi
Yung Hyun
YH
Yoo
Young Hyun
YH
Kim
Nam Deuk
ND
D017209:Apoptosis / Q000502:physiology*; D001647:Bile Acids and Salts / Q000737:chemistry / Q000502:physiology*; D002277:Carcinoma / Q000473:pathology*; D049109:Cell Proliferation; D002635:Chenodeoxycholic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004249:DNA Damage; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000502:physiology; D010766:Phosphorylation; D014407:Tumor Cells, Cultured; D014580:Ursodeoxycholic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D002583:Uterine Cervical Neoplasms / Q000473:pathology*
D001647:Bile Acids and Salts; C403900:HS 1183; C479128:HS 1200; C503536:HS-1199; D016328:NF-kappa B; D002635:Chenodeoxycholic Acid; D014580:Ursodeoxycholic Acid; D048031:JNK Mitogen-Activated Protein Kinases