Mountain grown ginseng induces apoptosis in HL-60 cells and its mechanism have little relation with TNF-alpha production.
The root of ginseng is one of the most popular natural tonics in Oriental countries. Ginseng grown in the wild, deep in the mountains, is known as Sansam (mountain grown ginseng, MGG). MGG belongs to Araliaceae and Panax. In this study, we investigated the effects of MGG on the cytotoxicity, induction of apoptosis and the putative pathways of its actions in human promyelocytic leukemia cells, HL-60. Using apoptosis analysis, we found that MGG is a potent inducer of apoptosis, but it has less effect on human peripheral blood mononuclear cells. Caspase-3 activation and subsequent apoptotic cell death in MGG-treated cells were partially blocked by the caspase-3 inhibitor, Z-DEVD-FMK. MGG also inhibited the caspase-8 activity. To determine whether MGG-induced apoptosis is involved in tumor necrosis factor-alpha (TNF-alpha) secretion, TNF-alpha secretion was quantified by enzyme-linked immunosorbent assay (ELISA) method. Unexpectedly, MGG significantly decreased the TNF-alpha secretion compared to the control. These results suggest that MGG-induced cytotoxicity have little relation with the secretion of TNF-alpha in HL-60 cells. Furthermore, MGG with rIFN-gamma synergistically increased nitric oxide (NO) production in mouse peritoneal macrophages. Taken together, our data indicate that MGG is a potent inducer of apoptosis on HL-60 cells and these abilities could be used clinically for the treatment of cancer.
Koo
Hyun-Na
HN
Department of Pharmacology, College of Oriental Medicine, Institute of Oriental Medicine, Kyung Hee University, 1 Hoegi-Dong, Dongdaemun-Gu, Seoul, Republic of Korea.
Jeong
Hyun-Ja
HJ
Choi
In-Young
IY
An
Hyo-Jin
HJ
Moon
Phil-Dong
PD
Kim
Seong-Jin
SJ
Jee
Seon-Young
SY
Um
Jae-Young
JY
Hong
Seung-Heon
SH
Shin
Soon-Shik
SS
Yang
Deok-Chun
DC
Seo
Yong-Suk
YS
Kim
Hyung-Min
HM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D061945:Caspase Inhibitors; D002478:Cells, Cultured; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004357:Drug Synergism; D018922:HL-60 Cells; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D005894:Panax; D010936:Plant Extracts / Q000494:pharmacology; D018517:Plant Roots; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D009842:Oligopeptides; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; C110772:benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; D009569:Nitric Oxide; D007371:Interferon-gamma; D053148:Caspase 3; D053181:Caspase 8