桑椹中矢车菊素-3-葡萄糖苷通过半胱天冬酶-3切割和DNA片段化在体内外的抗癌作用
Anti-cancer Effect of Cyanidin-3-glucoside from Mulberry via Caspase-3 Cleavage and DNA Fragmentation in vitro and in vivo.
作者信息
Cho Eugene, Chung Eun Y, Jang Hye-Yeon, Hong On-Yu, Chae Hee S, Jeong Young-Ju, Kim Sun-Young, Kim Byeong-Soo, Yoo Dong J, Kim Jong-Suk, Park Kwang-Hyun
机构信息
Department of Biochemistry and Institute of Cardiovascular Research, Chonbuk National University Medical School, Jeonju, 54896, Korea
Department of Anesthesiology and Pain Medicine,Bucheon St. Mary’s Hospital, the Catholic University of Korea, Bucheon 14647, Korea
出版信息
Anticancer Agents Med Chem. 2017 Nov 24;17(11):1519-1525. doi: 10.2174/1871520617666170327152026.
BACKGROUND
Fruits of Morus alba L. (mulberry) have various bioactive compounds such as polyphenols and anthocyanins and used as a herbal medicine. However, the anti-cancer effects and molecular basis have not been elucidated.
METHODS
We isolated the cyanidin-3-glucoside in various cultivar of mulberry by acidified-methanol extraction methods. This molecule were compared mass spectroscopic properties by LC-MS/MS and analyzed by 1H and 13C NMR. We examined the anti-cancer effect with molecular mechanisms of the cyanidin-3-glucoside on MDA-MB-453 human breast cancer cells and xenograft animal model.
RESULTS
The treatment with the mulberry cyanidin-3-glucoside decreased cell viability in a dose-dependent manner with alteration of apoptotic protein contents, and DNA fragmentation, suggesting that cells undergo apoptosis. Supporting the observations, Treatment with the cyanidin-3-glucoside showed active apoptosis by caspase-3 cleavage and DNA fragmentation through Bcl-2 and Bax pathway. Indeed, cyanidin-3-glucoside inhibits tumor growth in MDA-MB-453 cells-inoculated nude mice. Tumor growth of xenograft nude mouse was significantly reduced compared to the control group by the cyanidin-3-glucoside.
CONCLUSION
The data demonstrate that cyanidin-3-glucoside isolated from mulberry induced apoptosis in breast cancer (MDA-MB-453) cells, and therefore, has a potential as an anti-cancer agent. These results show that mulberry cyanidin-3-glucoside inhibit the proliferation and growth in vitro and in vivo model and, indicating the inhibition of tumor progression.
背景
桑(Morus alba L.)的果实含有多种生物活性化合物,如多酚和花青素,并被用作草药。然而,其抗癌作用及分子机制尚未阐明。
方法
我们通过酸化甲醇提取法从不同品种的桑中分离出矢车菊素 - 3 - 葡萄糖苷。通过液相色谱 - 串联质谱(LC - MS/MS)比较该分子的质谱特性,并通过1H和13C核磁共振(NMR)进行分析。我们研究了矢车菊素 - 3 - 葡萄糖苷对MDA - MB - 453人乳腺癌细胞和异种移植动物模型的抗癌作用及其分子机制。
结果
用桑矢车菊素 - 3 - 葡萄糖苷处理以剂量依赖性方式降低细胞活力,同时凋亡蛋白含量和DNA片段化发生改变,表明细胞发生凋亡。支持这些观察结果的是,用矢车菊素 - 3 - 葡萄糖苷处理通过半胱天冬酶 - 3切割以及通过Bcl - 2和Bax途径的DNA片段化显示出活跃的凋亡。事实上,矢车菊素 - 3 - 葡萄糖苷抑制接种了MDA - MB - 453细胞的裸鼠中的肿瘤生长。与对照组相比,矢车菊素 - 3 - 葡萄糖苷使异种移植裸鼠的肿瘤生长显著降低。
结论
数据表明,从桑中分离出的矢车菊素 - 3 - 葡萄糖苷可诱导乳腺癌(MDA - MB - 453)细胞凋亡,因此具有作为抗癌剂的潜力。这些结果表明,桑矢车菊素 - 3 - 葡萄糖苷在体外和体内模型中均抑制增殖和生长,表明其对肿瘤进展具有抑制作用。