Molecular mechanisms of exopolysaccharide from Aphanothece halaphytica (EPSAH) induced apoptosis in HeLa cells.
The present study aims to investigate the pharmacological effect of the exopolysaccharides from Aphanothece halophytica GR02 (EPSAH) on the HeLa human cervical cancer cell line. HeLa cells were cultured in RPMI-1640-10% FBS medium containing with or without different concentrations of EPSAH. Cell viability was assessed by methylthiazol tetrazolium (MTT) assay. Cell apoptosis was elevated with Wright-Giemsa staining, AO/EB double staining, and DNA fragmentation assay. Apoptosis-associated molecules from cultured HeLa cells were quantified using Western blot analysis. Our results suggest that EPASH induces apoptosis in HeLa cells by targeting a master unfolded protein response (UPR) regulator Grp78. Grp78 further promotes the expression of CHOP and downregulates expression of survivin, which leads to activate mitochondria-mediated downstream molecules and p53-survivin pathway, resulting in caspase-3 activation and causing apoptosis. These findings provide important clues for further evaluating the potential potency of EPSAH for use in cancer therapy.
School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
Yu
Y
Ou
School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
Shuya
S
Xu
School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
Dandan
D
Zhu
School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
Xuegan
X
Yang
D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D000458:Cyanobacteria / Q000254:growth & development / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D006367:HeLa Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D011134:Polysaccharides / Q000494:pharmacology*
D051017:Apoptosis Regulatory Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D011134:Polysaccharides; D020169:Caspases