PA-MSHA inhibits proliferation and induces apoptosis through the up-regulation and activation of caspases in the human breast cancer cell lines.
To investigate the effects of PA-MSHA (Pseudomonas aeruginosa-mannose sensitive hemagglutinin) on inhibiting proliferation of breast cancer cell lines and to explore its mechanisms of action in human breast cancer cells. MCF-10A, MCF-7, MDA-MB-468, and MDA-MB-231HM cells were treated with PA-MSHA or PA (Heat-killed P. aeruginosa) at different concentrations and different times. Changes of cell super-microstructure were observed by transmission electron microscopy. Cell cycle distribution and apoptosis induced by PA-MSHA were measured by flow cytometry (FCM) with PI staining, ANNEXIN V-FITC staining and Hoechst33258 staining under fluorescence microscopy. Western blot was used to evaluate the expression level of apoptosis-related molecules. A time-dependent and concentration-dependent cytotoxic effect of PA-MSHA was observed in MDA-MB-468 and MDA-MB-231HM cells but not in MCF-10A or MCF-7 cells. The advent of PA-MSHA changed cell morphology, that is to say, increases in autophagosomes, and vacuoles in the cytoplasm could also be observed. FCM with PI staining, ANNEXIN V-FITC and Hoechst33258 staining showed that the different concentrations of PA-MSHA could all induce the apoptosis and G(0)-G(1) cell cycle arrest of breast cancer cells. Cleaved caspase 3, 8, 9, and Fas protein expression levels were strongly associated with an increase in apoptosis of the breast cancer cells. There was a direct relationship with increased concentrations of PA-MSHA but not of PA. Completely different from PA, PA-MSHA may impart antiproliferative effects against breast cancer cells by inducing apoptosis mediated by at least a death receptor-related cell apoptosis signal pathway, and affecting the cell cycle regulation machinery.
Liu
Zhe-Bin
ZB
Department of Oncology, Breast Cancer Institute, Cancer Hospital, Shanghai Medical College, Institutes of Biomedical Science, Fudan University, Shanghai 200032, PR China.
Hou
Yi-Feng
YF
Di
Gen-Hong
GH
Wu
Jiong
J
Shen
Zhen-Zhou
ZZ
Shao
Zhi-Ming
ZM
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D006388:Hemagglutinins / Q000494:pharmacology* / Q000648:ultrastructure; D006801:Humans; D046529:Microscopy, Electron, Transmission; D011550:Pseudomonas aeruginosa / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation
D000970:Antineoplastic Agents; D006388:Hemagglutinins; D020169:Caspases