Abstract: Objective To investigate the effect of lonidamine on apoptosis of human breast carcinoma cells MCF-7 and the
possible mechanisms. Methods MTT assay and colony-forming assay were used to evaluate the growth inhibition induced by
lonidamine in breast cancer MCF-7 cells. PI/Annexin-V staining was used to detect the apoptotic cells. The ATP levels in the
cells were detected using an ATP assay kit. The expression of glucose regulated protein 78 (GRP78), inhibitor of apoptosis
protein (cIAP1) and caspase-8 were analyzed with Western blotting. Results MTT assay and colony-forming assay showed that
50-250 mmol/L lonidamine caused a time- and concentration-dependent inhibition of MCF-7 cell proliferation. Exposure to
increased concentrations of lonidamine resulted in significantly increased apoptosis rate in MCF-7 cells. In MCF-7 cells treated
with 50, 150 and 250 mmol/L lonidamine for 5 h, the intracellular ATP levels were lowered to 80.67%, 62.78% and 30.73% of the
control level, respectively. Western blotting showed that lonidamine up-regulated the expression of GRP78, down-regulated
the expression of cIAP1 and promoted caspase-8 activation as the treatment time extended. Conclusion Lonidamine can
inhibit the proliferation and induce apoptosis in MCF-7 cells, and these effects are probably mediated by reducing ATP level,
inducing endoplasmic reticulum stress response, down-regulating cIAP1, and promoting caspase-8 activation in the cells.