Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Breast Cancer Research
Published in: Breast Cancer Research 4/2006

Open Access 01-08-2006 | Research article

In vitrosynergistic cytoreductive effects of zoledronic acid and radiation on breast cancer cells

Authors: A Ugur Ural, Ferit Avcu, Muhammed Candir, Metin Guden, M Ali Ozcan

Published in: Breast Cancer Research | Issue 4/2006

Login to get access

Abstract

Introduction

Bisphosphonates are mostly used in the treatment of bone metastases. They have been shown to act synergistically with other chemotherapeutic agents. It is not known, however, whether similar synergistic effects exist with radiation on breast cancer cells.

Methods

Human MCF-7 breast cancer cells were treated with up to 100 μM zoledronic acid, were irradiated with up to 800 cGy or were exposed to combinations of both treatments to determine the antiproliferative effects of zoledronic acid and radiation.

Results

Zoledronic acid and radiation caused a dose-dependent and time-dependent decrease in cell viability (approximate 50% growth inhibition values were 48 μM and 20 μM for 24 hours and 72 hours, respectively, for zoledronic acid and 500 cGy for radiation). A synergistic cytotoxic effect of the combination of zoledronic acid and radiation was confirmed by isobologram analysis.

Conclusion

These data constitute the first in vitro evidence for synergistic effects between zoledronic acid and radiation. This combination therapy might thus be expected to be more effective than either treatment alone in patients with metastatic breast carcinoma.
Appendix
Available only for authorised users
Literature
1.
Lipton A: Management of bone metastases in breast cancer. Curr Treat Options Oncol. 2005, 6: 161-171.CrossRefPubMed
2.
3.
Sato M, Grasser W, Endo N, Akins R, Simmons H, Thompson DD, Golub E, Rodan GA: Bisphosphonate action. Alendronate localization in rat bone and effects on osteoclast ultrastructure. J Clin Invest. 1991, 88: 2095-2105.CrossRefPubMedPubMedCentral
4.
Ural AU, Yilmaz MI, Avcu F, Pekel A, Zerman M, Nevruz O, Sengul A, Yalcin A: The bisphosphonate zoledronic acid induces cytotoxicity in human myeloma cell lines with enhancing effects of dexamethasone and thalidomide. Int J Hematol. 2003, 78: 443-449.CrossRefPubMed
5.
Coxon FP, Thompson K, Rogers MJ: Recent advances in understanding the mechanism of action of bisphosphonates. Curr Opin Pharmacol. 2006, 6: 307-312. 10.1016/j.coph.2006.03.005.CrossRefPubMed
6.
Avcu F, Ural AU, Yilmaz MI, Ozcan A, Ide T, Kurt B, Yalcin A: The bisphosphonate zoledronic acid inhibits the development of plasmacytoma induced in BALB/c mice by intraperitoneal injection of pristane. Eur J Haematol. 2005, 74: 496-500. 10.1111/j.1600-0609.2005.00427.x.CrossRefPubMed
7.
Magnetto S, Boissier S, Delmas PD, Clezardin P: Additive antitumor activities of taxoids in combination with the bisphosphonate ibandronate against invasion and adhesion of human breast carcinoma cells to bone. Int J Cancer. 1999, 83: 263-269. 10.1002/(SICI)1097-0215(19991008)83:2<263::AID-IJC19>3.0.CO;2-T.CrossRefPubMed
8.
Van Der Pluijm G, Vloedgraven H, Van der Wee-Plas L, Lowik C, Papapoulos S: Bisphosphonates inhibit the adhesion of breast cancer cells to bone matrices in vitro. J Clin Invest. 1996, 98: 698-705.CrossRefPubMedPubMedCentral
9.
Rosen LS, Gordon D, Tchekmedyian S, Yanagihara R, Hirsh V, Krzakowski M, Pawlicki M, de Souza P, Zheng M, Urbanowitz G, et al: Zoledronic acid versus placebo in the treatment of skeletal metastases in patients with lung cancer and other solid tumors: a phase III, double-blind, randomized trial – the Zoledronic Acid Lung Cancer and Other Solid Tumors Study Group. J Clin Oncol. 2003, 21: 3150-3157. 10.1200/JCO.2003.04.105.CrossRefPubMed
10.
Rosen LS, Gordon DH, Dugan W, Major P, Eisenberg PD, Provencher L, Kaminski M, Simeone J, Seaman J, Chen BL, Coleman RE: Zoledronic acid is superior to pamidronate for the treatment of bone metastases in breast carcinoma patients with at least one osteolytic lesion. Cancer. 2004, 100: 36-43. 10.1002/cncr.11892.CrossRefPubMed
11.
Hoskin PJ, Stratford MR, Folkes LK, Regan J, Yarnold JR: Effect of local radiotherapy for bone pain on urinary markers of osteoclast activity. Lancet. 2000, 355: 1428-1429. 10.1016/S0140-6736(00)02144-9.CrossRefPubMed
12.
Vogt U, Bielawski KP, Bosse U, Schlotter CM: Breast tumour growth inhibition in vitro through the combination of cyclophosphamide/metotrexate/5-fluorouracil, epirubicin/cyclophosphamide, epirubicin/paclitaxel, and epirubicin/docetaxel with the bisphosphonates ibandronate and zoledronic acid. Oncol Rep. 2004, 12: 1109-1114.PubMed
13.
Tallarida RJ: Drug synergism: its detection and applications. J Pharmacol Exp Ther. 2001, 298: 865-872.PubMed
14.
Senaratne SG, Pirianov G, Mansi JL, Arnett TR, Colston KW: Bisphosphonates induce apoptosis in human breast cancer cell lines. Br J Cancer. 2000, 82: 1459-1468.CrossRefPubMedPubMedCentral
15.
Woodward JK, Neville-Webbe HL, Coleman RE, Holen I: Combined effects of zoledronic acid and doxorubicin on breast cancer cell invasion in vitro. Anticancer Drugs. 2005, 16: 845-854. 10.1097/01.cad.0000175582.01446.6f.CrossRefPubMed
16.
Jagdev SP, Coleman RE, Shipman CM, Rostami-H A, Croucher PI: The bisphosphonate, zoledronic acid, induces apoptosis of breast cancer cells: evidence for synergy with paclitaxel. Br J Cancer. 2001, 84: 1126-1134. 10.1054/bjoc.2001.1727.CrossRefPubMedPubMedCentral
17.
Stearns ME, Wang M: Effects of alendronate and taxol on PC-3 ML cell bone metastases in SCID mice. Invasion Metastasis. 1996, 16: 116-131.PubMed
18.
Neville-Webbe HL, Rostami-Hodjegan A, Evans CA, Coleman RE, Holen I: Sequence- and schedule-dependent enhancement of zoledronic acid induced apoptosis by doxorubicin in breast and prostate cancer cells. Int J Cancer. 2005, 113: 364-371. 10.1002/ijc.20602.CrossRefPubMed
19.
Algur E, Macklis RM, Hafeli UO: Synergistic cytotoxic effects of zoledronic acid and radiation in human prostate cancer and myeloma cell lines. Int J Radiat Oncol Biol Phys. 2005, 61: 535-542. 10.1016/j.ijrobp.2004.09.065.CrossRefPubMed
20.
Matsumoto S, Kimura S, Segawa H, Kuroda J, Yuasa T, Sato K, Nogawa M, Tanaka F, Maekawa T, Wada H: Efficacy of the third-generation bisphosphonate, zoledronic acid alone and combined with anti-cancer agents against small cell lung cancer cell lines. Lung Cancer. 2005, 47: 31-39. 10.1016/j.lungcan.2004.06.003.CrossRefPubMed
21.
Milas L, Hunter NR, Mason KA, Kurdoglu B, Peters LJ: Enhancement of tumor radioresponse of a murine mammary carcinoma by paclitaxel. Cancer Res. 1994, 54: 3506-3510.PubMed
22.
Sun J, Qian Y, Hamilton AD, Sebti SM: Ras CAAX peptidometric FTI 276 selectively blocks tumor growth in nude mice of a human lung carcinoma with K-Ras mutation and p53 deletion. Cancer Res. 1995, 55: 4243-4247.PubMed
23.
Li X, Liu L, Tupper JC, Bannerman DD, Winn RK, Sebti SM, Hamilton AD, Harlan JM: Inhibition of protein geranylgeranylation and RhoA/RhoA kinase pathway induces apoptosis in human endothelial cells. J Biol Chem. 2002, 277: 15309-15316. 10.1074/jbc.M201253200.CrossRefPubMed
24.
Salomo M, Jurlander J, Nielsen LB, Gimsing P: How myeloma cells escape bisphosphonate-mediated killing: development of specific resistance with preserved sensitivity to conventional chemotherapeutics. Br J Haematol. 2003, 122: 202-210. 10.1046/j.1365-2141.2003.04437.x.CrossRefPubMed
25.
McKenna WG, Muschel RJ: Targeting tumor cells by enhancing radiation sensitivity. Genes Chromosomes Cancer. 2003, 38: 330-338. 10.1002/gcc.10296.CrossRefPubMed
26.
Bernhard EJ, Kao G, Cox AD, Sebti SM, Hamilton AD, Muschel RJ, McKenna WG: The farnesyltransferase inhibitor FTI-277 radiosensitizes H-ras-transformed rat embryo fibroblasts. Cancer Res. 1996, 56: 1727-1730.PubMed
Metadata
Title
In vitrosynergistic cytoreductive effects of zoledronic acid and radiation on breast cancer cells
Authors
A Ugur Ural
Ferit Avcu
Muhammed Candir
Metin Guden
M Ali Ozcan
Publication date
01-08-2006
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 4/2006
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr1543

Other articles of this Issue 4/2006

Breast Cancer Research 4/2006 Go to the issue

Commentary

Stop! In the name of transforming growth factor-β: keeping estrogen receptor-α-positive mammary epithelial cells from proliferating

Research article

p53 protein accumulation predicts resistance to endocrine therapy and decreased post-relapse survival in metastatic breast cancer

Research article

Intrinsic molecular signature of breast cancer in a population-based cohort of 412 patients

Commentary

Single nucleotide polymorphisms and breast cancer: not yet a success story

Research article

The mTOR inhibitor rapamycin down-regulates the expression of the ubiquitin ligase subunit Skp2 in breast cancer cells

Research article

Comparison of gene expression profiles in core biopsies and corresponding surgical breast cancer samples
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits