A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / Zoledronic acid (ZA), the gold standard treatment for breast cancer‐derived osteolytic bone lesions, induces apoptosis in mature osteoclasts. Curcumin, a plant‐dervied component of turmeric (Curcuma longa), inhibits osteoclast differentiation. This study aimed to determine the in vitro and in vivo effects of ZA and curcuminoids, alone and combined, on osteoclast differentiation and survival, breast cancer cell growth, breast cancer cell‐induced osteolytic bone lesion area, and bone mineral density (BMD). Curcuminoids, but not ZA, inhibited osteoclast formation at doses that did not alter precursor viability, as assessed by osteoclastogenesis assays using murine RAW 264.7 cells. Combined curcuminoids and ZA did not differ from curcuminoids alone in their effects on osteoclast survival/formation. The half maximal inhibitory concentration (IC50) for ZA alone was 4 μM, while the IC50 for curcuminoids plus ZA was 6μM. Curcuminoids and ZA inhibit in vitro cell viability of human breast cancer‐ derived MDA‐MB‐231 cells, as assessed by MTT assays. The IC50 of ZA alone was projected to be 1.0677 x 10^4 μM, while the IC50 for curcuminoids alone (9.1 x 10^1 μM), was close to the IC50 for curcuminoids plus ZA (1.31 x 10^2 μM curcuminoids with 300 μM ZA). In vivo effects of ZA (2 μg/kg/d) and curcuminoids (25 mg/kg/d), alone and combined, on osteolytic bone lesions dervied from innoculation with MDA‐MB‐231 cells were assessed. Radiographically‐evident osteolytic bone lesion area did not differ between treatment groups, with a trend towards decreased osteolytic lesion area in mice treated with ZA. BMD In non‐responders, without bone or pericardiac tumors, assessed by dual energy x‐ray absorptiometry, was increased in mice administered ZA. Thus, for the first time, the combined in vitro effects of ZA and curcuminoids on osteclast formation and survival were demonstrated, as well as the combined effects of ZA and curcuminoids on bresat cancer‐derived osteolytic bone lesions and BMD.
| Identifer | oai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/531833 |
| Date | 13 April 2015 |
| Creators | Lukefahr, Ashley Leigh |
| Contributors | The University of Arizona College of Medicine - Phoenix, Funk, Janet MD, FACP |
| Publisher | The University of Arizona. |
| Source Sets | University of Arizona |
| Language | en_US |
| Detected Language | English |
| Type | Thesis |
| Rights | Copyright © is held by the author. Digital access to this material is made possible by the College of Medicine - Phoenix, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. |
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