Involvement of AMPK signaling cascade in capsaicin-induced apoptosis of HT-29 colon cancer cells.
Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is activated during ATP-depleting metabolic states, such as hypoxia, heat shock, oxidative stress, and exercise. As a highly conserved heterotrimeric kinase that functions as a major metabolic switch to maintain energy homeostasis, AMPK has been shown to exert as an intrinsic regulator of mammalian cell cycle. Moreover, AMPK cascade has emerged as an important pathway implicated in cancer control. In this article, we have investigated the effects of capsaicin on apoptosis in relation to AMPK activation in colon cancer cell. Capsaicin-induced apoptosis was revealed by the presence of nucleobodies in the capsaicin-treated HT-29 colon cancer cells. Concomitantly, the activation of AMPK and the increased expression of the inactive form of acetyl-CoA carboxylase (ACC) were detected in capsaicin-treated colon cancer cells. We showed that both capsaicin and 5'-aminoimidazole-4-carboxamide-1-beta-D-ribonucleoside (AICAR), an AMPK activator possess the AMPK-activating capacity as well as apoptosis-inducing properties. Evidence of the association between AMPK activation and the increased apoptosis in HT-29 colon cancer cells by capsaicin treatment, and further findings of the correlation of the activated AMPK and the elevated apoptosis by cotreatment of AICAR and capsaicin support AMPK as an important component of apoptosis, as well as a possible target of cancer control.
Kim
Young Min
YM
Department of Food and Nutrition, Hannam University, Daejeon 306-791, Korea.
Hwang
Jin-Taek
JT
Kwak
Dong Wook
DW
Lee
Yun Kyung
YK
Park
Ock Jin
OJ
D055372:AMP-Activated Protein Kinases; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002211:Capsaicin / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology*; D006131:Growth Inhibitors / Q000494:pharmacology; D019073:HT29 Cells; D006801:Humans; D009097:Multienzyme Complexes / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D012265:Ribonucleotides / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D006131:Growth Inhibitors; D009097:Multienzyme Complexes; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide; D002211:Capsaicin