Ghoneum Mamdooh, Gollapudi Sastry
Charles R. Drew University of Medicine and Science, Department of Otolaryngology, Los Angeles, CA 90059, USA.
Anticancer Res. 2004 May-Jun;24(3a):1455-63.
The present study was undertaken to evaluate the effect of phagocytosis of killed yeast on the induction of apoptosis in human metastatic breast cancer cells (MCF-7 and ZR-75-1) and non-metastatic breast cancer cells (HCC70). Heat-killed Saccharomyces cerevisiae, baker's and brewer's yeast, was cultured with cancer cells at a ratio of yeast to cancer cells = 10:1, and the percent apoptotic cancer cells was determined by flow cytometry and cytospin preparation. Upon phagocytosis of yeast, breast cancer cells underwent apoptosis. Induction of apoptosis was time- and dose-dependent. Apoptosis was detected as early as 0.5 h (13%), increased to 19% at 2 h and peaked (38%) at 4 h. Metastatic cancer cells were found to be more susceptible to yeast-induced apoptosis than non-metastatic cells; 629% increase for MCF-7 as compared to cells alone, 258% for ZR-75 cells, while HCC70 cells showed a 178% increase. Phagocytosis is associated with the disruption of mitochondrial membrane potential and activation of initiator and effector caspases 8, 9 and 3. However, inhibitors of these caspases did not inhibit yeast-induced apoptosis in cancer cells, suggesting that yeast induces apoptosis in breast cancer cells by a mechanism that is independent of caspase activation. This data may have clinical implications.
本研究旨在评估吞噬灭活酵母对人转移性乳腺癌细胞(MCF-7和ZR-75-1)和非转移性乳腺癌细胞(HCC70)凋亡诱导的影响。将热灭活的酿酒酵母、面包酵母和啤酒酵母与癌细胞按酵母与癌细胞10:1的比例培养,通过流式细胞术和细胞离心涂片法测定凋亡癌细胞的百分比。酵母被吞噬后,乳腺癌细胞发生凋亡。凋亡诱导呈时间和剂量依赖性。最早在0.5小时即可检测到凋亡(13%),2小时时增至19%,4小时时达到峰值(38%)。发现转移性癌细胞比非转移性细胞对酵母诱导的凋亡更敏感;与单独培养的细胞相比,MCF-7细胞增加了629%,ZR-75细胞增加了258%,而HCC70细胞增加了178%。吞噬作用与线粒体膜电位的破坏以及起始和效应半胱天冬酶8、9和3的激活有关。然而,这些半胱天冬酶的抑制剂并未抑制酵母诱导的癌细胞凋亡,这表明酵母通过一种独立于半胱天冬酶激活的机制诱导乳腺癌细胞凋亡。该数据可能具有临床意义。