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Arctigenin inhibits prostate tumor cell growth in vitro and in vivo

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1 Arctigenin inhibits prostate tumor cell growth in vitro and in vivo
Piwen Wang, Walter Solorzano, Tanya Diaz, Clara E. Magyar, Susanne M. Henning, Jaydutt V. Vadgama  Clinical Nutrition Experimental  Volume 13, Pages 1-11 (June 2017) DOI: /j.yclnex Copyright © 2017 The Authors Terms and Conditions

2 Fig. 1 In vitro anti-proliferative effect of arctigenin. (A) shows the chemical structure of Arc. Androgen sensitive LNCaP (B) and LAPC-4 (C) prostate cancer cells, prostate pre-malignant WPE1-NA22 cells (D), and normal prostate epithelial PrEC cells (E) were treated with the indicated concentrations of arctigenin for 48 h. Cell proliferation was measured by adenosine triphosphate (ATP) assay. Data are presented as mean ± SD. NT: non-treatment, DMSO control; Arc: arctigenin. Compared to NT, ∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001. Clinical Nutrition Experimental  , 1-11DOI: ( /j.yclnex ) Copyright © 2017 The Authors Terms and Conditions

3 Fig. 2 Inhibition of xenograft tumor growth, blood and tissue levels of arctigenin, and reduced expression of growth factors in SCID mice. Male SCID mice (n = 10 per group) were inoculated subcutaneously with 5 × 105 androgen-sensitive LAPC-4 prostate tumor cells. The intervention treatments started either one week after (A, B) or two weeks prior to (C, D) the tumor cell inoculation. Arctigenin was administered daily through oral gavage at dose of 50 mg/kg or 100 mg/kg bw. Tumor size was measured twice a week using calipers and tumor volume calculated using the formula: length×width×height× Tumor weight was measured at mouse sacrifice. Blood and tumor levels of arctigenin (E) was detected with HPLC coupled with CoulArray electrochemical detector after extraction with ethyl acetate. The concentrations of 8 growth factors in tumor tissues were simultaneously measured using a Human Growth Factor ELISA Strip II kit (F). Data are presented as mean ± SD. Arc: arctigenin. Compared to control, ∗P < 0.05, ∗∗P < 0.01. Clinical Nutrition Experimental  , 1-11DOI: ( /j.yclnex ) Copyright © 2017 The Authors Terms and Conditions

4 Fig. 3 Decreased Ki67 and AR and increased Bax/Bcl-2 ratio in tumor tissues by arctigenin treatment. A section of tumor tissue was formalin-fixed and paraffin-embedded for tissue microarray and immunohistochemical detection. Slides were cut and incubated with monoclonal antibodies for Ki67 and AR (A). Slides were counterstained with hematoxylin. Nuclei were stained in blue and Ki67 or AR in brown color. The positive rates of Ki67 nuclear staining, total and nuclear AR staining are presented as mean ± SD (B). The protein expression of Bax and Bcl-2 in tumor tissues was detected by Western blot. Four representative protein bands from each group are demonstrated (C). The ratios of Bax to Bcl-2 are presented as mean ± SD (D). Arc: arctigenin. Compared to control, ∗P < 0.05, ∗∗P < 0.01. Clinical Nutrition Experimental  , 1-11DOI: ( /j.yclnex ) Copyright © 2017 The Authors Terms and Conditions

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