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Silibinin inhibits accumulation of myeloid-derived suppressor cells and tumor growth of murine breast cancer.

Forghani P, Khorramizadeh MR, Waller EK - Cancer Med (2014)

Bottom Line: Silibinin, a natural flavonoid from the seeds of milk thistle, has been developed as an anti-inflammatory agent and supportive care agent to reduce the toxicity of cancer chemotherapy.The effects of silibinin on 4T1 cell viability in vitro were measured by BLI.The antitumor activity of silibinin requires an intact host immune system and is associated with decreased accumulation of blood and tumor-associated MDSCs.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran; Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia.

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Silibinin has limited in vitro antiproliferative activity in 4T1 cells 4T1-luc tumor cells were seeded in triplicates in 96-well plates at a concentration of 105–106/well with media containing silibinin. The top row represents untreated cells in triplicate, and the two bottom rows represent treated cells in increasing concentrations of silibinin from left to right in duplicate. After 24 h luciferin was added to the medium and ROI measured in each well. (A) Graph represents total flux collected in well from three independent experiments. (B) Logarithmic graph represents of total flux of tumors versus different concentrations of silibinin. The horizontal axis shows concentration of silibinin.
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fig03: Silibinin has limited in vitro antiproliferative activity in 4T1 cells 4T1-luc tumor cells were seeded in triplicates in 96-well plates at a concentration of 105–106/well with media containing silibinin. The top row represents untreated cells in triplicate, and the two bottom rows represent treated cells in increasing concentrations of silibinin from left to right in duplicate. After 24 h luciferin was added to the medium and ROI measured in each well. (A) Graph represents total flux collected in well from three independent experiments. (B) Logarithmic graph represents of total flux of tumors versus different concentrations of silibinin. The horizontal axis shows concentration of silibinin.

Mentions: Given evidence that MDSCs development begins in the bone marrow microenvironment 29, we evaluated the number of MDSCs in BM from nontumor-bearing mice after prolonged administration (2 months) of silibinin treatment. Treatment began every other day for the first month and then weekly for a second month. Contrary to the significant reduction in MDSCs numbers in the blood of silibinin-treated tumor-bearing mice, we did not find any significant difference in the numbers of MDSCs in BM or blood of nontumor-bearing mice following silibinin treatment (data not shown). Silibinin has been shown to have direct cytotoxic effects on tumor cells in vitro 21,31,32. To explore the mechanism by which silibinin decreased tumor growth in mice, we tested whether silibinin has a direct effect on 4T1 cell viability in vitro. 4T1 cells were treated at 60–70% confluency with different concentrations of silibinin for 24 h. Tumor viability was measured by BLI, as luciferase activity represents the number and viability of metabolically active 4T1–luciferase cells, and luciferase activity was not observed in apoptotic 4T1 cells or lysate prepared from 4T1 cells. On the basis of total flux, the metabolic activity of viable tumor cell line showed only a modest decrease following treatment with graduated levels of silibinin (Fig. 3 A and B).


Silibinin inhibits accumulation of myeloid-derived suppressor cells and tumor growth of murine breast cancer.

Forghani P, Khorramizadeh MR, Waller EK - Cancer Med (2014)

Silibinin has limited in vitro antiproliferative activity in 4T1 cells 4T1-luc tumor cells were seeded in triplicates in 96-well plates at a concentration of 105–106/well with media containing silibinin. The top row represents untreated cells in triplicate, and the two bottom rows represent treated cells in increasing concentrations of silibinin from left to right in duplicate. After 24 h luciferin was added to the medium and ROI measured in each well. (A) Graph represents total flux collected in well from three independent experiments. (B) Logarithmic graph represents of total flux of tumors versus different concentrations of silibinin. The horizontal axis shows concentration of silibinin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3987072&req=5

fig03: Silibinin has limited in vitro antiproliferative activity in 4T1 cells 4T1-luc tumor cells were seeded in triplicates in 96-well plates at a concentration of 105–106/well with media containing silibinin. The top row represents untreated cells in triplicate, and the two bottom rows represent treated cells in increasing concentrations of silibinin from left to right in duplicate. After 24 h luciferin was added to the medium and ROI measured in each well. (A) Graph represents total flux collected in well from three independent experiments. (B) Logarithmic graph represents of total flux of tumors versus different concentrations of silibinin. The horizontal axis shows concentration of silibinin.
Mentions: Given evidence that MDSCs development begins in the bone marrow microenvironment 29, we evaluated the number of MDSCs in BM from nontumor-bearing mice after prolonged administration (2 months) of silibinin treatment. Treatment began every other day for the first month and then weekly for a second month. Contrary to the significant reduction in MDSCs numbers in the blood of silibinin-treated tumor-bearing mice, we did not find any significant difference in the numbers of MDSCs in BM or blood of nontumor-bearing mice following silibinin treatment (data not shown). Silibinin has been shown to have direct cytotoxic effects on tumor cells in vitro 21,31,32. To explore the mechanism by which silibinin decreased tumor growth in mice, we tested whether silibinin has a direct effect on 4T1 cell viability in vitro. 4T1 cells were treated at 60–70% confluency with different concentrations of silibinin for 24 h. Tumor viability was measured by BLI, as luciferase activity represents the number and viability of metabolically active 4T1–luciferase cells, and luciferase activity was not observed in apoptotic 4T1 cells or lysate prepared from 4T1 cells. On the basis of total flux, the metabolic activity of viable tumor cell line showed only a modest decrease following treatment with graduated levels of silibinin (Fig. 3 A and B).

Bottom Line: Silibinin, a natural flavonoid from the seeds of milk thistle, has been developed as an anti-inflammatory agent and supportive care agent to reduce the toxicity of cancer chemotherapy.The effects of silibinin on 4T1 cell viability in vitro were measured by BLI.The antitumor activity of silibinin requires an intact host immune system and is associated with decreased accumulation of blood and tumor-associated MDSCs.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran; Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia.

Show MeSH
Related in: MedlinePlus