Estradiol impairs the antiproliferative and proapoptotic effect of Zoledronic acid in hormone sensitive breast cancer cells in vitro

• Published in: PloS one 2017-09, Vol.12 (9), p.e0185566-e0185566
• Main Authors: Gschwantler-Kaulich, Daphne, Weingartshofer, Sigrid, Grunt, Thomas W, Mairhofer, Mario, Tan, Yen, Gamper, Jutta, Singer, Christian F
• Format: Article
• Language: English
• Subjects: 17β-Estradiol; Acids; Anticancer properties; Antineoplastic Agents - administration & dosage; Antiproliferatives; Antitumor activity; Apoptosis; Apoptosis - drug effects; Biology and Life Sciences; Biotechnology; Bone cancer; Bone density; Bone Density Conservation Agents - administration & dosage; Bone Density Conservation Agents - antagonists & inhibitors; Bone Neoplasms - prevention & control; Bone Neoplasms - secondary; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer; Cancer therapies; Cell Cycle - drug effects; Cell death; Cell Line, Tumor; Cell proliferation; Cell Proliferation - drug effects; Charcoal; Chemotherapy; Complications and side effects; Deoxyribonucleic acid; Development and progression; Diphosphonates - administration & dosage; Diphosphonates - antagonists & inhibitors; DNA; DNA, Neoplasm - biosynthesis; Dosage and administration; Drug therapy; Estradiol; Estradiol - administration & dosage; Estradiol - adverse effects; Estrogens; Female; Flow cytometry; Gynecology; Health risk assessment; Humans; Imidazoles - administration & dosage; Imidazoles - antagonists & inhibitors; In vitro methods and tests; MCF-7 Cells; Medical statistics; Medicine and Health Sciences; Metastases; Metastasis; Neoplasms, Hormone-Dependent - drug therapy; Neoplasms, Hormone-Dependent - metabolism; Neoplasms, Hormone-Dependent - pathology; Obstetrics; Penicillin; Physiological aspects; Post-menopause; Research and analysis methods; Sex hormones; Tumor cell lines; Tumors; Zoledronic acid
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0185566

Zoledronic acid (ZA) has antiresorptive effects and protects from bone metastasis in women with early breast cancer. In addition, in postmenopausal women with endocrine responsive breast cancer ZA prolongs DFS. The exact mechanism is still unclear. We have therefore investigated the effect of increasing concentrations of ZA in breast cancer cell lines in the absence or presence of estradiol to mimic the hormonal environment in vitro. Using assays for cell proliferation (EZ4U, BrdU) and cell death (Annexin/PI), we have analyzed the dose-dependent antiproliferative and pro-apoptotic effects of ZA in two hormone sensitive cell lines (MCF-7 and T47D) and a hormone insensitive, triple negative cell line (MDA-MB-231) in the presence of 0, 1 and 10 nM estradiol. In the absence of estradiol, ZA exerts dose-dependent antiproliferative and pro-apoptotic antitumor effects in both, hormone sensitive (MCF-7, T47D) and -insensitive (MDA-MB-231) breast cancer cell lines (p