title: The effects of bufadienolides on HER2 overexpressing breast cancer cells.
abstract: 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.
authors.affiliation: Institute of Cancer Stem Cell, Dalian Medical University Cancer Center, Dalian, China.
authors.forename: Tianjiao
authors.initials: T
authors.lastname: Wang
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Mu
authors.affiliation: Institute of Cancer Stem Cell, Dalian Medical University Cancer Center, Dalian, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Jin
authors.affiliation: Institute of Cancer Stem Cell, Dalian Medical University Cancer Center, Dalian, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Institute of Cancer Stem Cell, Dalian Medical University Cancer Center, Dalian, China.
authors.forename: Yueyue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian, China.
authors.forename: Xiaochi
authors.initials: X
authors.lastname: Ma
authors.affiliation: Institute of Cancer Stem Cell, Dalian Medical University Cancer Center, Dalian, China. jinjinpan11@126.com.
authors.forename: Jinjin
authors.initials: J
authors.lastname: Pan
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, China. miaojiancndl@aliyun.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Miao
authors.affiliation: Institute of Cancer Stem Cell, Dalian Medical University Cancer Center, Dalian, China. yuhuiyuan@hotmail.com.
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Yuan
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D002018:Bufanolides / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D000090063:Proto-Oncogene Mas; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: D002018:Bufanolides; D000090063:Proto-Oncogene Mas; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; C000715470:MAS1 protein, human; C087925:bufadienolide
keywords: Breast cancer; HER2; SRC-1; SRC-3