Semaan Josiane, El-Hakim Sandy, Ibrahim José-Noel, Safi Rémi, Elnar Arpiné Ardzivian, El Boustany Charbel
Department of Laboratory Science, Faculty of Public Health-Branch 2, CERIPH (Center of Studies and Research in Public Health), Lebanese University, Pierre Gemayel Campus in Fanar, Beirut, Lebanon.
Department of Anatomy, Cell Biology and Physiological Science, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Breast Cancer. 2020 Jul;27(4):696-705. doi: 10.1007/s12282-020-01063-6. Epub 2020 Feb 24.
Short-chain fatty acids (SCFAs) are ubiquitous lipids produced as a result of bacterial fermentation of dietary fiber. While their role in colorectal cancer is well known, the effect of SCFAs in breast cancer is poorly defined.
To understand the various effects of SCFAs on breast carcinogenesis, we investigated the effect of sodium butyrate (NaB) and sodium propionate (NaP) in MCF-7 cell line.
Cells were incubated with different concentrations of NaB or NaP for 24, 48, 72 or 96 h. Cell proliferation was assayed using MTT kit. Cell cycle was performed using propidium iodide staining then analyzed with a flow cytometer. Apoptosis was assessed by Hoechst technique and cell-cycle sub-G1 phase.
NaB and NaP inhibited MCF-7 cell proliferation in a dose-dependent manner with respective IC of 1.26 mM and 4.5 mM, thus indicating that NaB is more potent than NaP. Low and medium levels of both SCFAs induced morphology changes which are characteristic of a differentiated phenotype. Flow cytometry analysis revealed a blockage in G1 growth phase. Interestingly, removing NaB or NaP from culture media after few days of treatment showed a reversible effect on cell morphology and proliferation where cells reentered the cycle after 24 h of drug wash-out. Finally, treatment with medium levels of these molecules induced low MCF-7 apoptosis, while higher doses led to massive apoptosis.
Our results show that SCFAs may be considered as an interesting inhibitor for breast cancer progression.
短链脂肪酸(SCFAs)是膳食纤维细菌发酵产生的普遍存在的脂质。虽然它们在结直肠癌中的作用已广为人知,但SCFAs在乳腺癌中的作用却尚不明确。
为了解SCFAs对乳腺癌发生的各种影响,我们研究了丁酸钠(NaB)和丙酸钠(NaP)对MCF-7细胞系的影响。
将细胞与不同浓度的NaB或NaP孵育24、48、72或96小时。使用MTT试剂盒检测细胞增殖。采用碘化丙啶染色进行细胞周期分析,然后用流式细胞仪进行分析。通过Hoechst技术和细胞周期亚G1期评估细胞凋亡。
NaB和NaP以剂量依赖方式抑制MCF-7细胞增殖,其各自的半数抑制浓度分别为1.26 mM和4.5 mM,这表明NaB比NaP更有效。低水平和中等水平的两种SCFAs均诱导了具有分化表型特征的形态变化。流式细胞术分析显示G1生长阶段受阻。有趣的是,在处理几天后从培养基中去除NaB或NaP对细胞形态和增殖显示出可逆作用,在药物洗脱24小时后细胞重新进入细胞周期。最后,用中等水平的这些分子处理诱导了低水平的MCF-7细胞凋亡,而更高剂量则导致大量细胞凋亡。
我们的结果表明,SCFAs可能被认为是一种有趣的乳腺癌进展抑制剂。