Betulinic Acid Suppresses Breast Cancer Metastasis by Targeting GRP78-Mediated Glycolysis and ER Stress Apoptotic Pathway

Figure 3

BA suppresses metastasis through β-catenin-mediated glycolysis. (a) The transcription levels of metastasis-related genes were screened by qPCR after BA treatment. Almost all genes were suppressed, among which β-catenin ranked as the most repressed gene in both cell lines (the results were obtained from triplicate experiments and were represented as ; as compared with control). (b) Western blotting further confirmed that β-catenin and its downstream target c-Myc were downregulated by BA in a dose-dependent manner. (c) BA dramatically attenuated the levels of glycolysis-related proteins including LDHA and p-PDK1/PDK, whereas LDHB was elevated due to its function of converting lactate into pyruvate. (d) BA reduced the lactate production of MDA-MB-231 and BT-549 cells in a dose-dependent manner (values were represented as ; and as compared with control). (e) The cell energy phenotype was profiled by the extracellular flux analyzer. BA reduced ECAR and OCR values, keeping breast cancer cells in a relative quiescent energetic state.

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