title: Apoptosis of AGS human gastric adenocarcinoma cells by methanolic extract of Dictamnus.
abstract: BACKGROUND
  The root bark of Dictamnus dasycarpus Turcz has traditionally been used in East Asia to treat skin diseases such as eczema, atopic dermatitis, and psoriasis. However, it has also been reported to exhibit an anti-proliferative effect on cancer cells.
  
  
  OBJECTIVE
  To investigate the anti-cancer effects of a methanol extract of Dictamnus dasycarpus root bark (MEDD) on AGS cells (a human gastric adenocarcinoma cell-line).
  
  
  METHODS
  An 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium assay, a caspase activity assay, cell cycle analysis, mitochondrial membrane potential (MMP) measurements, and western blotting were used to investigate the anti-cancer effects of MEDD on AGS cells.
  
  
  RESULTS
  Treatment with MEDD significantly and concentration-dependently inhibited AGS cell growth. MEDD treatment in AGS cells led to increased accumulation of apoptotic sub-G1 phase cells in a concentration-dependent manner. Also, MEDD reduced the expressions of pro-caspase-3, -8 and -9, and increased the active form of caspase-3. Furthermore, subsequent Western blotting revealed elevated levels of poly (ADP-ribose) polymerase protein. MEDD treatment reduced levels of MMP and anti-apoptotic Bcl-2 and Bcl-xL proteins. Pretreatment with SB203580 (a specific inhibitor of p38 mitogen-activated protein kinases), SP600125 (a potent inhibitor of C-Jun N-terminal kinases), or PD98059 (a potent inhibitor of extracellular signal-regulated kinases) did not modify the effects of MEDD treatment. However, pretreatment with LY294002 (a specific inhibitor of Akt) significantly enhanced MEDD-induced cell death.
  
  
  CONCLUSIONS
  These results suggest that MEDD-mediated cell death is associated with the intrinsic apoptotic pathway and that inhibition of Akt signaling contributes to apoptosis induction by MEDD.
authors.affiliation: Division of Longevity and Biofunctional Medicine, Healthy Aging Korean Medical Research Center, Yangsan 626-870, Republic of Korea.
authors.forename: Hyun Soo
authors.initials: HS
authors.lastname: Park
authors.affiliation: Division of Longevity and Biofunctional Medicine, Healthy Aging Korean Medical Research Center, Yangsan 626-870, Republic of Korea.
authors.forename: Noo Ri
authors.initials: NR
authors.lastname: Hong
authors.affiliation: Division of Longevity and Biofunctional Medicine, Healthy Aging Korean Medical Research Center, Yangsan 626-870, Republic of Korea.
authors.forename: Tae Seok
authors.initials: TS
authors.lastname: Ahn
authors.affiliation: Division of Pharmacology, School of Korean Medicine, Pusan National University, Yangsan 626-870, Republic of Korea.
authors.forename: Hyungwoo
authors.initials: H
authors.lastname: Kim
authors.affiliation: Division of Longevity and Biofunctional Medicine, Healthy Aging Korean Medical Research Center, Yangsan 626-870, Republic of Korea.
authors.forename: Myeong Ho
authors.initials: MH
authors.lastname: Jung
authors.affiliation: Division of Longevity and Biofunctional Medicine, Healthy Aging Korean Medical Research Center, Yangsan 626-870, Republic of Korea.
authors.forename: Byung Joo
authors.initials: BJ
authors.lastname: Kim
keywords: A human gastric adenocarcinoma cell-line; Akt; Dictamnus dasycarpus; LY294002; apoptosis; gastric cancer