Chrysanthemum morifolium Ramat sensitizes TNF-related apoptosis inducing ligand-induced apoptosis in human colon cancer cell line DLD-1

AIM: To explore the influence of Chrysanthemum morifolium Ramat on TNF-related apoptosis inducing ligand (TRAIL)-mediated apoptosis in human colon cancer cell line DLD-1 and its possible mechanism. METHODS: Adenovirus-mediated TRAIL gene AD/hTERT-gTRAIL was applied either alone or by combination with Chrysanthemum morifolium Ramat in human colon DLD-1 cell line. Cell growth and apoptosis were measured by inverted microscope, MTT method and flow cytometry. The expression of TRAIL mRNA, TRAIL-Rs mRNA and TRAIL protein expression after exposure to Chrysanthemum morifolium Ramat were measured by semi-quantitive RT-PCR and FACS, respectively. RESULTS: The suppression percentages and apoptotic rate of DLD-1 by Ad/hTERT-gTRAIL alone were 31.4% and 13.5%, respectively. Combination of TRAIL gene transfection with Chrysanthemum morifolium Ramat, the suppression and the apoptosis rate raised to 93.1% and 45.4%, respectively (P<0.05). The expression of TRAIL mRNA was upregulated from 0.46 to 1.01 by Chrysanthemum morifolium Ramat (P<0.05). The percentage of TRAIL protein expression increased from 2.2% to 5.0%. DR4 mRNA and DR5 mRNA were upregulated from 0.70, 0.22 to 1.10, 0.83, respectively (P<0.01), while DcR1 mRNA, DcR2 mRNA were downregulated from 1.60, 1.15 to 0.19, 0.78, respectively (P<0.05). CONCLUSIONS: Ad/hTERT-gTRAIL induced apoptosis in DLD-1.Combination of Chrysanthemum morifolium Ramat with Ad/hTERT-gTRAIL enhanced the effect. The upregulation of TRAIL death receptors as well as the downregulation of TRAIL decoy receptors may play an important role.