AM251 suppresses the viability of HepG2 cells through the AMPK (AMP-activated protein kinase)-JNK (c-Jun N-terminal kinase)-ATF3 (activating transcription factor 3) pathway.
AM251, a cannabinoid antagonist, has various biological activities. In this study, we found that AM251 suppressed the viability of hepatoma HepG2 cells and also increased phosphorylation of JNK (c-jun N-terminal kinase) and ATF3 (activating transcription factor 3). In addition, AM251 phosphorylated AMPK (AMP-activated protein kinase) in a time and dose-dependent manner. Inhibition of AMPK blocked AM251-induced JNK/ATF3 phosphorylation. Expression of AMPK or treatment with AICAR (5-aminoimidazole-4-carboxy-amide-1-d-ribofuranoside), an AMPK activator, activated the JNK/ATF3 pathways. Together, these results suggest that AM251 may have anti-tumor effects in hepatoma through activation of the AMPK-JNK-ATF3 signal pathway.
Lee
Yun Mi
YM
Department of Anatomy, Korea University College of Medicine, 126-1, 5 ga, Anam-dong, Seongbuk-gu, Seoul 136-701, South Korea.
Uhm
Kyung-Ok
KO
Lee
Eun Soo
ES
Kwon
Joseph
J
Park
Sun Hwa
SH
Kim
Hyeon Soo
HS
D055372:AMP-Activated Protein Kinases; D051700:Activating Transcription Factor 3 / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002186:Cannabinoids / Q000037:antagonists & inhibitors; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology*; D012265:Ribonucleotides / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
D051700:Activating Transcription Factor 3; D000970:Antineoplastic Agents; D002186:Cannabinoids; D009097:Multienzyme Complexes; D010880:Piperidines; D011720:Pyrazoles; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; C103505:AM 251; D017346:Protein Serine-Threonine Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide