Luo Ke-Wang, Ko Chun-Hay, Yue Grace Gar-Lee, Lee Julia Kin-Ming, Li Kai-Kai, Lee Michelle, Li Gang, Fung Kwok-Pui, Leung Ping-Chung, Lau Clara Bik-San
Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
Discipline of Orthopaedics and Trauma, University of Adelaide, Adelaide, SA, Australia.
J Nutr Biochem. 2014 Apr;25(4):395-403. doi: 10.1016/j.jnutbio.2013.11.013. Epub 2013 Dec 31.
Green tea (Camellia sinensis, CS), a kind of Chinese tea commonly consumed as a healthy beverage, has been demonstrated to have various biological activities, including antioxidation, antiobesity and anticancer. Our study aims to investigate the antitumor, antimetastasis and antiosteolytic effects of CS aqueous extract both in vitro and in vivo using metastasis-specific mouse mammary carcinoma 4T1 cells. Our results showed that treatment of 4T1 cells with CS aqueous extract resulted in significant inhibition of 4T1 cell proliferation. CS extract induced 4T1 apoptosis in a dose-dependent manner as assessed by annexin-V and propidium iodide staining and caspase-3 activity. Western blot analysis showed that CS increased the expression of Bax-to-Bcl-2 ratio and activated caspase-8 and caspase-3 to induce apoptosis. CS also inhibited 4T1 cell migration and invasion at 0.06-0.125 mg/ml. In addition, CS extract (0.6 g/kg, orally fed daily for 4 weeks) was effective in decreasing the tumor weight by 34.8% in female BALB/c mice against water treatment control (100%). Apart from the antitumor effect, CS extract significantly decreased lung and liver metastasis in BALB/c mice bearing 4T1 tumors by 54.5% and 72.6%, respectively. Furthermore, micro-computed tomography and in vitro osteoclast staining analysis suggested that CS extract was effective in bone protection against breast cancer-induced bone destruction. In conclusion, the present study demonstrated that the CS aqueous extract, which closely mimics green tea beverage, has potent antitumor and antimetastasis effects in breast cancer and could protect the bone from breast cancer-induced bone destruction.
绿茶(茶树,CS)是一种作为健康饮品广泛饮用的中国茶,已被证明具有多种生物活性,包括抗氧化、抗肥胖和抗癌作用。我们的研究旨在利用转移特异性小鼠乳腺癌4T1细胞,在体外和体内研究CS水提取物的抗肿瘤、抗转移和抗骨溶解作用。我们的结果表明,用CS水提取物处理4T1细胞可显著抑制4T1细胞增殖。通过膜联蛋白-V和碘化丙啶染色以及半胱天冬酶-3活性评估,CS提取物以剂量依赖性方式诱导4T1细胞凋亡。蛋白质印迹分析表明,CS增加了Bax与Bcl-2的比值表达,并激活了半胱天冬酶-8和半胱天冬酶-3以诱导凋亡。CS在0.06 - 0.125 mg/ml时也抑制4T1细胞迁移和侵袭。此外,CS提取物(0.6 g/kg,每天口服给药4周)对雌性BALB/c小鼠的肿瘤重量有显著降低作用,相对于水处理对照组(100%)降低了34.8%。除了抗肿瘤作用外,CS提取物还显著降低了携带4T1肿瘤的BALB/c小鼠的肺转移和肝转移,分别降低了54.5%和72.6%。此外,微型计算机断层扫描和体外破骨细胞染色分析表明,CS提取物对预防乳腺癌诱导骨破坏具有有效的骨保护作用。总之,本研究表明,与绿茶饮品成分相近的CS水提取物在乳腺癌中具有强大的抗肿瘤和抗转移作用,并能保护骨骼免受乳腺癌诱导的骨破坏。