Coffee decoction enhances tamoxifen proapoptotic activity on MCF-7 cells.
Coffee decoction enhances tamoxifen proapoptotic activity on MCF-7 cells.
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DOI：
10.1038/s41598-020-76445-z
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发表时间：
2020-11-11
影响因子：
4.6
通讯作者：
Tamura H
中科院分区：
文献类型：
--
作者：
Funakoshi-Tago M;Tago K;Li C;Hokimoto S;Tamura H
咖啡的消费被认为可以有效地增强他莫昔芬对乳腺癌的治疗效果；然而，其潜在的分子机制仍不清楚。在此，我们试图通过雌激素受体α(ERα)阳性的乳腺癌细胞株MCF-7来阐明咖啡煎剂如何与他莫昔芬协同发挥抗癌作用。结果表明，咖啡因抑制ERα的转录可能是咖啡因下调ER DNA表达的机制之一。咖啡煎剂与三苯氧胺协同作用可诱导细胞周期停滞和细胞死亡，其机制可能是通过降低细胞周期蛋白D1的表达和激活抑癌基因P53来实现的。咖啡煎液中含有咖啡因是诱导细胞周期停滞和细胞死亡的必要条件，但不充分，提示咖啡煎液中的未知化合物(S)需要减少细胞周期蛋白D1的表达，并激活包括P53在内的细胞凋亡信号转导通路。通过这些未知成分(S)、咖啡因和他莫昔芬的协同作用激活P53似乎是由于抑制了ERK和Akt通路。尽管抑制这些途径诱导P53介导的细胞凋亡的机制尚不清楚，但脱咖啡因、咖啡因和他莫昔芬的组合也引起了细胞周期停滞和细胞凋亡，这表明脱咖啡因咖啡中存在的未知化合物(S)与咖啡因和他莫昔芬有协同作用。
The consumption of coffee has been suggested to effectively enhance the therapeutic effects of tamoxifen against breast cancer; however, the underlying molecular mechanisms remain unclear. We herein attempted to clarify how coffee decoction exerts anti-cancer effects in cooperation with tamoxifen using the estrogen receptor α (ERα)-positive breast cancer cell line, MCF-7. The results obtained showed that coffee decoction down-regulated the expression of ERα, which was attributed to caffeine inhibiting its transcription. Coffee decoction cooperated with tamoxifen to induce cell-cycle arrest and apoptotic cell death, which may have been mediated by decreases in cyclin D1 expression and the activation of p53 tumor suppressor. The inclusion of caffeine in coffee decoction was essential, but not sufficient, to induce cell-cycle arrest and apoptotic cell death, suggesting the requirement of unknown compound(s) in coffee decoction to decrease cyclin D1 expression and activate apoptotic signaling cascades including p53. The activation of p53 through the cooperative effects of these unidentified component(s), caffeine, and tamoxifen appeared to be due to the suppression of the ERK and Akt pathways. Although the mechanisms by which the suppression of these pathways induces p53-mediated apoptotic cell death remain unclear, the combination of decaffeinated coffee, caffeine, and tamoxifen also caused cell-cycle arrest and apoptotic cell death, suggesting that unknown compound(s) present in decaffeinated coffee cooperate with caffeine and tamoxifen.
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影响因子：
4.2
作者：
Allred, Kimberly F.;Yackley, Katarina M.;Allred, Clinton D.
通讯作者：
Allred, Clinton D.
DOI：
10.1093/jnci/86.17.1297
发表时间：
1994-09-07
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
FLORENES, VA;MAELANDSMO, GM;FODSTAD, O
通讯作者：
FODSTAD, O
DOI：
10.1073/pnas.1018858109
发表时间：
2012-10-30
影响因子：
11.1
作者：
Bailey, Shannon T.;Shin, Hyunjin;Brown, Myles
通讯作者：
Brown, Myles
影响因子：
45.3
作者：
Harvey, JM;Clark, GM;Allred, DC
通讯作者：
Allred, DC
影响因子：
6.2
作者：
CUNHA, GR
通讯作者：
CUNHA, GR