Growth inhibitory and antimetastatic effect of green tea polyphenols on metastasis-specific mouse mammary carcinoma 4T1 cells in vitro and in vivo systems (Publication with Expression of Concern. See vol. 24, pg. 6103, 2018)
Growth inhibitory and antimetastatic effect of green tea polyphenols on metastasis-specific mouse mammary carcinoma 4T1 cells in vitro and in vivo systems (Publication with Expression of Concern. See vol. 24, pg. 6103, 2018)
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DOI：
10.1158/1078-0432.ccr-04-1976
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发表时间：
2005-03-01
影响因子：
11.5
通讯作者：
Kadiyar, SK
中科院分区：
文献类型：
--
作者：
Baliga, MS;Meleth, S;Kadiyar, SK
目的：乳腺癌是女性癌症相关死亡的第二大原因。饮食习惯也可能在乳腺癌风险和预防中发挥作用。在此，我们研究了绿色茶多酚（GTP）在体外和体内系统中对高转移性小鼠乳腺癌4 TI细胞的生长和转移的影响。用（-）表没食子儿茶素-3-没食子酸酯（EGCG）处理4 T1细胞，并测定对细胞增殖、诱导凋亡、促凋亡和Bcl-2家族的抗凋亡蛋白的影响，以及在3-（4，5-二甲基噻唑-2-基）-2，5-二苯基溴化四唑、流式细胞术和蛋白质印迹分析之后的胱天蛋白酶3和聚（ADP-核糖）聚合酶活化。结果：EGCG能抑制4 T1细胞增殖，诱导4 T1细胞凋亡，并呈剂量和时间依赖性。凋亡的增加伴随着Bcl-2蛋白表达的减少，同时Bax、细胞色素c释放、Apaf-1以及caspase 3和PARP蛋白的裂解增加。饮用富含EGCG的GTP水治疗荷4 TI细胞的BALB/c小鼠导致肿瘤生长减少，同时肿瘤中Bax/Bcl-2比值增加，增殖细胞核抗原减少和caspase 3活化。绿色茶治疗后，肿瘤细胞肺转移受到抑制，动物生存期延长。结论：本研究提示GTP具有预防乳腺癌发生和转移的作用，但其分子靶点还需进一步的体内研究。
Purpose: Breast cancer is the second leading cause of cancer-related deaths among females. Dietary habits may have a role in breast cancer risk and prevention as well. Here, we examined the effect of green tea polyphenols (GTP) on growth and metastasis of highly metastatic mouse mammary carcinoma 4TI cells in vitro and in vivo systems.Experimental Design: 4T1 cells were treated with (-) epigallocatechin-3-gallate (EGCG), and the effect was determined on cellular proliferation, induction of apoptosis, proapoptosis, and antiapoptotic proteins of Bcl-2 family, and caspase 3 and poly(ADP-ribose) polymerase activation following 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry, and Western blot analysis. Anticarcinogenic and antimetastatic effect of GTP in 4T1 cells was assessed in immunocompetent BALB/c mice.Results: Treatment of 4T1 cells with EGCG resulted in inhibition of cell proliferation, induction of apoptosis in doseand time-dependent manner. The increase in apoptosis was accompanied with decrease in the protein expression of Bcl-2 concomitantly increase in Bax, cytochrome c release, Apaf-1, and cleavage of caspase 3 and PARP proteins. Treatment of EGCG-rich GTP in drinking water to 4TI cells bearing BALB/c mice resulted in reduction of tumor growth accompanied with increase in Bax/Bcl-2 ratio, reduction in proliferating cell nuclear antigen and activation of caspase 3 in tumors. Metastasis of tumor cells to lungs was inhibited and survival period of animals was increased after green tea treatment.Conclusion: This study suggests that GTP have the ability to prevent the development of breast cancer and its metastasis; however, further in vivo studies are required to identify the molecular targets.