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Zoledronic acid increases anti‐angiogenic factors in an osteotropic breast cancer cell line
Author(s) -
Morshedian Shaghayegh,
Contreras Cynthia,
Bush Jason A.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb206
Subject(s) - zoledronic acid , bisphosphonate , cancer research , bone resorption , breast cancer , bone metastasis , osteoclast , cytotoxicity , cancer , cancer cell , cyr61 , chemistry , medicine , osteoporosis , biochemistry , receptor , in vitro , growth factor , ctgf
Bone is the most common organ for tumor metastasis in breast cancer patients. Currently, bisphosphonates are a main‐stay of cancer treatment known to reduce and/or delay the skeletal related events of malignancy by impairing osteoclast‐mediated bone resorption. The purpose of this project was to define differences between the breast cancer cell line, MDA‐MB‐231, and an osteotropic clone, MDA‐231BO, in response to the bisphosphonate, zoledronic acid (ZOL). Results demonstrate that MDA‐231BO cells are more sensitive to ZOL cytotoxicity and the salutary effects are both media‐ and calcium‐dependent, as elevating exogenous calcium levels increased ZOL cytotoxicity. To investigate possible mechanisms of ZOL‐induced cell death, total RNA, whole protein lysates, or mitochondrial‐enriched fractions were isolated from treated MDA‐231BO cells and compared to non‐treated controls. Using semi‐quantitative RT‐PCR, ZOL‐treated cells exhibited a down‐regulation of CYR61, a matricellular protein over‐expressed in highly invasive cancers while using a combination of 2D‐PAGE separation and MALDI‐MS/MS, we report the identification of a small subset of differentially‐expressed proteins including an up‐regulation of anti‐angiogenic proteins. Taken together, our results provide a better understanding of the molecular mechanism associated with ZOL exposure in osteotropic cancer cells.