Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Mar;11(3):1783-1790.
doi: 10.3892/ol.2016.4153. Epub 2016 Jan 26.

Laricitrin suppresses increased benzo(a)pyrene-induced lung tumor-associated monocyte-derived dendritic cell cancer progression

Wei-An Chang  1 , Jen-Yu Hung  2 , Ying-Ming Tsai  3 , Ya-Ling Hsu  4 , Hung-Hsing Chiang  5 , Shah-Hwa Chou  6 , Ming-Shyan Huang  2 , Po-Lin Kuo  7
Affiliations

Laricitrin suppresses increased benzo(a)pyrene-induced lung tumor-associated monocyte-derived dendritic cell cancer progression

Wei-An Chang et al. Oncol Lett. 2016 Mar.

Abstract

Benzo(a)pyrene (BaP) stimulates lung cancer cells, promoting monocyte-derived dendritic cells to secrete soluble factors, including heparin binding-epidermal growth factor and C-X-C motif chemokine 5. The secretions from monocyte-derived dendritic cells stimulate the progression of lung cancer cells, including the migration and invasion of cells. To the best of our knowledge, these secretions remain unknown, and require additional study. The present study identified that treatment with BaP-H1395-tumor-associated dendritic cell-conditioned medium had the most marked effect on cell migration and invasion. This result may be associated with the female gender, stage 2 adenocarcinoma or mutation of the proto-oncogene B-Raf (BRAF), according to the cell line background. Laricitrin, a dietary flavonoid derivative present in grapes and red wine, suppresses certain factors and decreases the progression of lung cancer cells that are promoted by BaP in the lung cancer tumor microenvironment. The results of the present study suggest that prolonged exposure to BaP exacerbates lung cancer, particularly in female lung cancer patients with the BRAF mutation, but that laricitrin may ameliorate this effect.

Keywords: benzo(a)pyrene; laricitrin; lung cancer; tumor microenvironment.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Flow chart of the production of various CM. (A) Flow chart of the production of control-CM, H1395-CM, BaP-H1395-CM, H1975-CM, BaP-H1975-CM, H2087-CM, BaP-H2087-CM, HCC2935-CM, and BaP-HCC2935-CM. (B) Flow chart of the production of mdDC-CM, H1395-TADC-CM, BaP-H1395-TADC-CM, H1975-TADC-CM, BaP-H1975-TADC-CM, H2087-TADC-CM, BaP-H2087-TADC-CM, HCC2935-TADC-CM and BaP-HCC2935-TADC-CM. CM, conditioned media; BaP, benzo(a)pyrene; mcDC, monocyte-derived dendritic cell; TADC, tumor-associated dendritic cell; IL-4, interleukin 4; GM-CSF, granulocyte macrophage-colony-stimulating factor; IFN-γ, interferon-γ; LPS, lipopolysaccharide.
Figure 2.
Figure 2.
CM of BaP-treated lung cancer cells did not cause mdDCs to enhance lung cancer cell proliferation. (A) Comparison between the proliferation of H1395 cells cultured in BaP-H1395-TADC-CM and H1395-TADC-CM. (B) Comparison between the proliferation of H1975 cells cultured in BaP-H1975-TADC-CM and H1975-TADC-CM. (C) Comparison between the proliferation of H2087 cells cultured in BaP-H2087-TADC-CM and H2087-TADC-CM. (D) Comparison between the proliferation of HCC2935 cells cultured in BaP-HCC2935-TADC-CM and HCC2935-TADC-CM. The data are expressed as the mean ± standard deviation of 3 independent experiments. *P<0.05 vs. mdDC-CM treatment. CM, conditioned media; BaP, benzo(a)pyrene; mdDC, monocyte-derived dendritic cells; TADC, tumor-associated dendritic cell.
Figure 3.
Figure 3.
CM of BaP-treated lung cancer caused mdDCs to enhance lung cancer cell migration. (A) Comparison between the migration of H1395 cells cultured in BaP-H1395-TADC-CM and H1395-TADC-CM. (B) Comparison between the migration of H1975 cells cultured in BaP-H1975-TADC-CM and H1975-TADC-CM. (C) Comparison between the migration of H2087 cells cultured in BaP-H2087-TADC-CM and H2087-TADC-CM. (D) Comparison between the migration of HCC2935 cells cultured in BaP-HCC2935-TADC-CM and HCC2935-TADC-CM. The data are expressed as the mean ± standard deviation of 3 independent experiments. *P<0.05 vs. mdDC-CM treatment; #P<0.05 vs. TADC-CM treatment. CM, conditioned media; BaP, benzo(a)pyrene; mdDC, monocyte-derived dendritic cell; TADC, tumor-associated dendritic cell; OD, optical density.
Figure 4.
Figure 4.
CM of BaP-treated lung cancer caused mdDCs to exacerbate lung cancer cell invasion. (A) Comparison between the invasion of H1395 cells cultured in BaP-H1395-TADC-CM and H1395-TADC-CM. (B) Comparison between the invasion of H1975 cells cultured in BaP-H1975-TADC-CM and H1975-TADC-CM. (C) Comparison between the invasion of H2087 cells cultured in BaP-H2087-TADC-CM and H2087-TADC-CM. (D) Comparison between the invasion of HCC2935 cells cultured in BaP-HCC2935-TADC-CM and HCC2935-TADC-CM. The data are expressed as the mean ± standard deviation of 3 independent experiments. *P<0.05 vs. mdDC-CM treatment; #P<0.05 vs. TADC-CM treatment. CM, conditioned media; BaP, benzo(a)pyrene; mdDC, monocyte-derived dendritic cell; TADC, tumor-associated dendritic cell; OD, optical density.
Figure 5.
Figure 5.
Laricitrin suppresses BaP-mediated cancer aggravation in the lung cancer tumor microenvironment. The effect of laricitrin on the (A) proliferation, (B) migration and (C) invasion of i) H1395 and ii) HCC2935 cells in the TADC-CM or BaP-TADC-CM cultures. The data are expressed as the mean ± standard deviation of 3 independent experiments. *P<0.05 vs. TADC-CM treatment; #P<0.05 vs. BaP-TADC-CM treatment. CM, conditioned medium; BaP, benzo(a)pyrene; mdDC, monocyte-derived dendritic cell; TADC, tumor associated dendritic cell; OD, optical density.
Figure 6.
Figure 6.
Laricitrin reverses benzo(a)pyrene-associated lung cancer aggravation in the lung cancer tumor microenvironment.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225–249. doi: 10.3322/caac.20006. - DOI - PubMed
    1. Tsai MJ, Chang WA, Huang MS, Kuo PL. Tumor microenvironment: A new treatment target for cancer. ISRN Biochem. 2014;2014:351959. doi: 10.1155/2014/351959. - DOI - PMC - PubMed
    1. Hsu YL, Huang MS, Cheng DE, Hung JY, Yang CJ, Chou SH, Kuo PL. Lung tumor-associated dendritic cell-derived amphiregulin increased cancer progression. J Immunol. 2011;187:1733–1744. doi: 10.4049/jimmunol.1100996. - DOI - PubMed
    1. Kuo CH, Chen KF, Chou SH, Huang YF, Wu CY, Cheng DE, Chen YW, Yang CJ, Hung JY, Huang MS. Lung tumor-associated dendritic cell-derived resistin promoted cancer progression by increasing Wolf-Hirschhorn syndrome candidate 1/Twist pathway. Carcinogenesis. 2013;34:2600–2609. doi: 10.1093/carcin/bgt281. - DOI - PubMed
    1. Kuo PL, Huang MS, Hung JY, Chou SH, Chiang SY, Huang YF, Yang CJ, Tsai MJ, Chang WA, Hsu YL. Synergistic effect of lung tumor-associated dendritic cell-derived HB-EGF and CXCL5 on cancer progression. Int J Cancer. 2014;135:96–108. doi: 10.1002/ijc.28673. - DOI - PubMed

LinkOut - more resources