dc.contributor.author |
Park Young-Eun |
|
dc.contributor.author |
Bava Usha |
|
dc.contributor.author |
Lin Jian-Ming |
|
dc.contributor.author |
Cornish Jillian |
|
dc.contributor.author |
Naot Dorit |
|
dc.contributor.author |
Reid Ian R |
|
dc.date.accessioned |
2020-11-05T22:41:57Z |
|
dc.date.available |
2020-11-05T22:41:57Z |
|
dc.date.issued |
2019-11 |
|
dc.identifier.issn |
0171-967X |
|
dc.identifier.uri |
http://hdl.handle.net/2292/53456 |
|
dc.description.abstract |
Bisphosphonates are used in treating patients with breast cancer. In vitro studies have shown that bisphosphonates act directly on tumour cells, inhibiting cell proliferation and inducing apoptosis. In most such studies, drugs were added to culture media exposing cells to high bisphosphonate concentrations in solution. However, since bisphosphonates bind to bone hydroxyapatite with high affinity and remain bound for very long periods of time, these experimental systems are not an optimal model for the action of the drugs in vivo. The aim of this study was to determine whether bone-bound zoledronate has direct effects on adjacent breast cancer cells. Bone slices were pre-incubated with bisphosphonate solutions, washed, and seeded with cells of the breast cancer cell lines, MCF7 or MDA-MB-231. Proliferation was assessed by cell counts and thymidine incorporation for up to 72 h. Inhibition of the mevalonate pathway was tested by measuring the levels of unprenylated Rap1A, and apoptosis was examined by the presence of cleaved caspase-8 on western blots. The proliferation rate of breast cancer cells on zoledronate-treated bone was significantly lower compared to cells on control bone. Other bisphosphonates showed a similar inhibitory effect, with an order of potency similar to their clinical potencies. Unprenylated Rap1A accumulated in MCF7 cells on zoledronate-treated bone, suggesting zoledronate acted through the inhibition of the mevalonate pathway. Accumulation of cleaved caspase-8 in MDA-MB-231 cells on bisphosphonate-treated bone indicated increased apoptosis in the cells. In conclusion, bone-bound zoledronate inhibits breast cancer cell proliferation, an activity that may contribute to its clinical anti-tumour effects. |
|
dc.format.medium |
Print-Electronic |
|
dc.language |
eng |
|
dc.publisher |
SPRINGER |
|
dc.relation.ispartofseries |
Calcified tissue international |
|
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
|
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
|
dc.subject |
1112 Oncology and Carcinogenesis |
|
dc.subject |
Biomedical |
|
dc.subject |
Basic Science |
|
dc.subject |
Breast Cancer |
|
dc.subject |
Cancer |
|
dc.subject |
Cancer |
|
dc.subject |
2.1 Biological and endogenous factors |
|
dc.subject |
Science & Technology |
|
dc.subject |
Life Sciences & Biomedicine |
|
dc.subject |
Endocrinology & Metabolism |
|
dc.subject |
Bisphosphonates |
|
dc.subject |
Breast cancer cells |
|
dc.subject |
Zoledronates |
|
dc.subject |
Bone-bound zoledronate |
|
dc.subject |
MCF7 |
|
dc.subject |
MDA-MB-231 |
|
dc.subject |
NITROGEN-CONTAINING BISPHOSPHONATES |
|
dc.subject |
S-PHASE ARREST |
|
dc.subject |
ZOLEDRONIC ACID |
|
dc.subject |
INDUCE APOPTOSIS |
|
dc.subject |
PROSTATE-CANCER |
|
dc.subject |
LUNG-CANCER |
|
dc.subject |
3RD-GENERATION BISPHOSPHONATE |
|
dc.subject |
ADJUVANT BISPHOSPHONATE |
|
dc.subject |
POSTMENOPAUSAL WOMEN |
|
dc.subject |
MEVALONATE PATHWAY |
|
dc.subject |
1103 Clinical Sciences |
|
dc.subject |
0601 Biochemistry And Cell Biology |
|
dc.subject |
0903 Biomedical Engineering |
|
dc.title |
Bone-Bound Bisphosphonates Inhibit Proliferation of Breast Cancer Cells. |
|
dc.type |
Journal Article |
|
dc.identifier.doi |
10.1007/s00223-019-00590-5 |
|
pubs.issue |
5 |
|
pubs.begin-page |
497 |
|
pubs.volume |
105 |
|
dc.date.updated |
2020-10-08T21:34:16Z |
|
dc.rights.holder |
Copyright: The author |
en |
pubs.author-url |
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000490290100005&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=6e41486220adb198d0efde5a3b153e7d |
|
pubs.end-page |
505 |
|
pubs.publication-status |
Published |
|
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Research Support, Non-U.S. Gov't |
|
pubs.subtype |
Journal Article |
|
pubs.elements-id |
461946 |
|
dc.identifier.eissn |
1432-0827 |
|