bufadienolide and Breast-Neoplasms

HER2 is a proto-oncogene frequently amplified in human breast cancer, its overexpression is correlated with tamoxifen resistance and decreased recurrence-free survival. Arenobufagin and bufalin are homogeneous bufadienolides of cardiac glycosides agents. In this research, we studied the effects of arenobufagin and bufalin on cellular survival and proliferation of HER2 overexpressing breast cancer cells and the mechanism under the results including the direct effect on HER2 downstream pathways. Our results showed that arenobufagin and bufalin could significantly inhibit the proliferation and survival of HER2 overexpressing breast cancer cells, along with the declination of SRC-1, SRC-3, nuclear transcription factor E2F1, phosphorylated AKT, and ERK. And the combination of each bufadienolide in low dose with tamoxifen could significantly enhance the inhibitory effect of tamoxifen on HER2 overexpressing breast cancer cells. All above suggest that arenobufagin and bufalin may be potential therapy adjuvants for HER2 overexpressing breast cancer therapy.

Topics: Apoptosis; Blotting, Western; Breast Neoplasms; Bufanolides; Cell Cycle; Cell Proliferation; Female; Gene Expression Regulation, Neoplastic; Humans; Phosphorylation; Proto-Oncogene Mas; Proto-Oncogene Proteins c-akt; Receptor, ErbB-2; Signal Transduction; Tumor Cells, Cultured