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Ginsenosides and their role in modulating TNF‐alpha signaling to enhance apoptosis in MDA‐MB 231 breast cancer cells
Author(s) -
Hantak Alison M,
Murphy Laura L
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.717.1
Subject(s) - apoptosis , tumor necrosis factor alpha , programmed cell death , viability assay , chemistry , pharmacology , cancer research , necrosis , population , medicine , biochemistry , environmental health
The aim of the present study was to determine if ginsenosides enhance tumor necrosis factor‐ (TNF‐α) induced apoptosis through modulation of TNF‐α signaling pathways. MDA‐MB 231 breast cancer cells were treated with 0.5 mg/ml of ginsenoside fraction (GF), 12.5 ug/ml of the ginsenoside metabolite Rh2, or 100 ng/ml of TNF‐α, alone or in combination, for 24 hours. The inclusion of GF or Rh2 together with TNF‐α increased percentage of cell death, but all three in combination further enhanced this effect. Flow cytometric analysis showed that GF or Rh2 with TNF‐α induced a G0/G1 arrest, while GF+TNF+Rh2 produced a robust increase in the pre‐G0/G1 cell population relative to other treatments. Further co‐treatment with a pan caspase inhibitor (Z‐VAD‐FMK) indicated that treatment‐induced cell death is caspase dependent. To analyze the role of TNF‐α in this system, proteins were collected at 15, 30, and 60 minutes after treatment and analyzed for phosphorylated levels of IkB and JNK. TNF‐α stimulated these downstream targets, but GF and Rh2 together with TNF‐α diminished this effect. Cells were then pretreated with inhibitors of NFκB (PDTC) or JNK (SP60012), resulting in further cell death. Together, these results suggest that GF and Rh2, alone or in combination, can enhance the apoptotic activities of TNF‐α by modulating the activities of downstream pro‐survival factors. (Supported by CA121074)