S. cerevisiae induces apoptosis in human metastatic breast cancer cells by altering intracellular Ca2+ and the ratio of Bax and Bcl-2.
We have recently demonstrated that non-metastatic human breast cancer cell lines undergo apoptosis following phagocytosis of S. cerevisiae. In this study, we investigated the apoptotic effect of heat-killed yeast against human metastatic breast cancer (MBC) cells, MDA-MB-231 in vitro, and the underlying mechanistic bases of this effect. Results show that monolayer MDA-MB-231 cells phagocytized yeast (50% at 16 h) and underwent apoptosis (32% compared with 7.6% of untreated cells, representing a 4.2-fold increase). The increase in apoptosis was associated with an elevation of [Ca2+]I. Addition of 2-aminoethoxydiphenyl borate (2APB), a pharmacological inhibitor of Ca2+ release from the endoplasmic reticulum, effectively diminished yeast-induced apoptosis. Furthermore, yeast caused a substantial decrease in expression of Bcl-2 and an increase in Bax resulting in alteration in the Bax:Bcl-2 ratio. However, yeast had no effect on NO levels. In conclusion, yeast induces apoptosis of human MBC cells in vitro by a mechanism involving intracellular Ca2+ and Bax:Bcl-2.
Ghoneum
Mamdooh
M
Department of Otolaryngology, Charles Drew University of Medicine and Science, Los Angeles, CA 90059, USA. mghoneum@ucla.edu
Matsuura
Motohiro
M
Braga
Melissa
M
Gollapudi
Sastry
S
D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D010587:Phagocytosis / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D002118:Calcium