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Antitumor activity of total flavonoids from Tetrastigma hemsleyanum Diels et Gilg is associated with the inhibition of regulatory T cells in mice.

Feng Z, Hao W, Lin X, Fan D, Zhou J - Onco Targets Ther (2014)

Bottom Line: The effects of total flavonoids on tumor growth in vivo were examined.Flow cytometry was used to study the effects on Tregs, and enzyme-linked immunosorbent assay was used to analyze the changes in the serum levels of transforming growth factor β, prostaglandin E2, and cyclooxygenase 2 after tumor inoculation and flavonoid administration.Total flavonoids from T. hemsleyanum Diels et Gilg may be used as antitumor agents in cancer prevention and treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, People's Republic of China ; Department of Oncology, Guang An Men Hospital, China Academy of Chinese Medical Sciences, Beijing, People's Republic of China.

ABSTRACT

Objective: To determine the antitumor activity of Radix tetrastigmae flavonoids and their inhibitory effect on regulatory T cells (Tregs) in mice.

Materials and methods: Total flavonoids were isolated from Radix tetrastigmae, the root of Tetrastigma hemsleyanum Diels et Gilg, and administered to C57BL/6 mice by oral gavage after inoculation with Lewis lung carcinoma (LLC) cells. The effects of total flavonoids on tumor growth in vivo were examined. Flow cytometry was used to study the effects on Tregs, and enzyme-linked immunosorbent assay was used to analyze the changes in the serum levels of transforming growth factor β, prostaglandin E2, and cyclooxygenase 2 after tumor inoculation and flavonoid administration.

Results: Total flavonoids from T. hemsleyanum Diels et Gilg significantly inhibited tumor growth in C57BL/6 mice inoculated with LLCs. These flavonoids dramatically suppressed regulatory T-cell development in tumor-bearing mice. Further studies revealed that total flavonoids significantly decreased the serum levels of transforming growth factor β, prostaglandin E2, and cyclooxygenase 2 in tumor-bearing mice, which may be responsible for the inhibition of Tregs.

Conclusion: The antitumor activity of total flavonoids from T. hemsleyanum Diels et Gilg is associated with the inhibition of Tregs in a mouse tumor model. Total flavonoids from T. hemsleyanum Diels et Gilg may be used as antitumor agents in cancer prevention and treatment.

No MeSH data available.


Related in: MedlinePlus

Flow cytometry analysis of regulatory T cells in mice.Notes: Peripheral blood leukocytes and splenocytes were stained with fluorescein isothiocyanate (FITC)-conjugated anti-mouse CD4 and phycoerythrin-conjugated anti-mouse CD25. After cell fixation, the cells were treated with allophycocyanin (APC)-conjugated anti-mouse Foxp3. Then, the cells were analyzed by flow cytometry for determination of regulatory T cell quantity. Representative data showing FITC-conjugated CD4-staining cells are presented in peripheral blood leukocytes from mice without flavonoid administration (A) and with 15 mg/kg flavonoid administration (B) after Lewis lung carcinoma tumor inoculation. Representative data showing allophycocyanin-conjugated FoxP3-staining cells are also shown in peripheral blood leukocytes from mice without flavonoid administration (C) and with flavonoid administration (D) and are used in the gating for CD4+CD25+ regulatory T cells in peripheral blood leukocytes from mice without flavonoid administration (E) and with flavonoid administration (F).
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f4-ott-7-947: Flow cytometry analysis of regulatory T cells in mice.Notes: Peripheral blood leukocytes and splenocytes were stained with fluorescein isothiocyanate (FITC)-conjugated anti-mouse CD4 and phycoerythrin-conjugated anti-mouse CD25. After cell fixation, the cells were treated with allophycocyanin (APC)-conjugated anti-mouse Foxp3. Then, the cells were analyzed by flow cytometry for determination of regulatory T cell quantity. Representative data showing FITC-conjugated CD4-staining cells are presented in peripheral blood leukocytes from mice without flavonoid administration (A) and with 15 mg/kg flavonoid administration (B) after Lewis lung carcinoma tumor inoculation. Representative data showing allophycocyanin-conjugated FoxP3-staining cells are also shown in peripheral blood leukocytes from mice without flavonoid administration (C) and with flavonoid administration (D) and are used in the gating for CD4+CD25+ regulatory T cells in peripheral blood leukocytes from mice without flavonoid administration (E) and with flavonoid administration (F).

Mentions: Because flavonoids from Radix Tetrastigmae could inhibit tumor growth in mice (Figures 2 and 3), and Tregs play a critical role in the suppression of antitumor immunity,12,13,17 we aimed to investigate whether flavonoids could inhibit Treg development in mice. Tregs were defined as CD25+ and FoxP3+ CD4+ T cells (Figure 4) and can inhibit the functions of other CD4 T cells and cytotoxic CD8 T cells by means of cell–cell contact or secretion of the inhibitory cytokines interleukin 10 and TGF-β.16 The results showed that flavonoids from Radix Tetrastigmae significantly reduced Treg number in peripheral blood leukocytes (Figures 4E, F and 5A) and, at higher doses, decreased Treg number in the spleen as well (Figure 5B). The results suggested that flavonoids from Radix Tetrastigmae suppress Treg development, and thus inhibit tumor growth in mice.


Antitumor activity of total flavonoids from Tetrastigma hemsleyanum Diels et Gilg is associated with the inhibition of regulatory T cells in mice.

Feng Z, Hao W, Lin X, Fan D, Zhou J - Onco Targets Ther (2014)

Flow cytometry analysis of regulatory T cells in mice.Notes: Peripheral blood leukocytes and splenocytes were stained with fluorescein isothiocyanate (FITC)-conjugated anti-mouse CD4 and phycoerythrin-conjugated anti-mouse CD25. After cell fixation, the cells were treated with allophycocyanin (APC)-conjugated anti-mouse Foxp3. Then, the cells were analyzed by flow cytometry for determination of regulatory T cell quantity. Representative data showing FITC-conjugated CD4-staining cells are presented in peripheral blood leukocytes from mice without flavonoid administration (A) and with 15 mg/kg flavonoid administration (B) after Lewis lung carcinoma tumor inoculation. Representative data showing allophycocyanin-conjugated FoxP3-staining cells are also shown in peripheral blood leukocytes from mice without flavonoid administration (C) and with flavonoid administration (D) and are used in the gating for CD4+CD25+ regulatory T cells in peripheral blood leukocytes from mice without flavonoid administration (E) and with flavonoid administration (F).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061169&req=5

f4-ott-7-947: Flow cytometry analysis of regulatory T cells in mice.Notes: Peripheral blood leukocytes and splenocytes were stained with fluorescein isothiocyanate (FITC)-conjugated anti-mouse CD4 and phycoerythrin-conjugated anti-mouse CD25. After cell fixation, the cells were treated with allophycocyanin (APC)-conjugated anti-mouse Foxp3. Then, the cells were analyzed by flow cytometry for determination of regulatory T cell quantity. Representative data showing FITC-conjugated CD4-staining cells are presented in peripheral blood leukocytes from mice without flavonoid administration (A) and with 15 mg/kg flavonoid administration (B) after Lewis lung carcinoma tumor inoculation. Representative data showing allophycocyanin-conjugated FoxP3-staining cells are also shown in peripheral blood leukocytes from mice without flavonoid administration (C) and with flavonoid administration (D) and are used in the gating for CD4+CD25+ regulatory T cells in peripheral blood leukocytes from mice without flavonoid administration (E) and with flavonoid administration (F).
Mentions: Because flavonoids from Radix Tetrastigmae could inhibit tumor growth in mice (Figures 2 and 3), and Tregs play a critical role in the suppression of antitumor immunity,12,13,17 we aimed to investigate whether flavonoids could inhibit Treg development in mice. Tregs were defined as CD25+ and FoxP3+ CD4+ T cells (Figure 4) and can inhibit the functions of other CD4 T cells and cytotoxic CD8 T cells by means of cell–cell contact or secretion of the inhibitory cytokines interleukin 10 and TGF-β.16 The results showed that flavonoids from Radix Tetrastigmae significantly reduced Treg number in peripheral blood leukocytes (Figures 4E, F and 5A) and, at higher doses, decreased Treg number in the spleen as well (Figure 5B). The results suggested that flavonoids from Radix Tetrastigmae suppress Treg development, and thus inhibit tumor growth in mice.

Bottom Line: The effects of total flavonoids on tumor growth in vivo were examined.Flow cytometry was used to study the effects on Tregs, and enzyme-linked immunosorbent assay was used to analyze the changes in the serum levels of transforming growth factor β, prostaglandin E2, and cyclooxygenase 2 after tumor inoculation and flavonoid administration.Total flavonoids from T. hemsleyanum Diels et Gilg may be used as antitumor agents in cancer prevention and treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, People's Republic of China ; Department of Oncology, Guang An Men Hospital, China Academy of Chinese Medical Sciences, Beijing, People's Republic of China.

ABSTRACT

Objective: To determine the antitumor activity of Radix tetrastigmae flavonoids and their inhibitory effect on regulatory T cells (Tregs) in mice.

Materials and methods: Total flavonoids were isolated from Radix tetrastigmae, the root of Tetrastigma hemsleyanum Diels et Gilg, and administered to C57BL/6 mice by oral gavage after inoculation with Lewis lung carcinoma (LLC) cells. The effects of total flavonoids on tumor growth in vivo were examined. Flow cytometry was used to study the effects on Tregs, and enzyme-linked immunosorbent assay was used to analyze the changes in the serum levels of transforming growth factor β, prostaglandin E2, and cyclooxygenase 2 after tumor inoculation and flavonoid administration.

Results: Total flavonoids from T. hemsleyanum Diels et Gilg significantly inhibited tumor growth in C57BL/6 mice inoculated with LLCs. These flavonoids dramatically suppressed regulatory T-cell development in tumor-bearing mice. Further studies revealed that total flavonoids significantly decreased the serum levels of transforming growth factor β, prostaglandin E2, and cyclooxygenase 2 in tumor-bearing mice, which may be responsible for the inhibition of Tregs.

Conclusion: The antitumor activity of total flavonoids from T. hemsleyanum Diels et Gilg is associated with the inhibition of Tregs in a mouse tumor model. Total flavonoids from T. hemsleyanum Diels et Gilg may be used as antitumor agents in cancer prevention and treatment.

No MeSH data available.


Related in: MedlinePlus