Zoledronic acid (Zometa) enhances the cytotoxic effect of gemcitabine and fluvastatin: in vitro isobologram studies with conventional and nonconventional cytotoxic agents

Oncology
Daniel R Budman, Anthony Calabro

Abstract

To identify synergistic combinations of clinically available agents with zoledronic acid which would enhance antitumor activity as measured by median effect isobologram analysis and apoptosis assays in vitro. The interaction of zoledronic acid as a doublet with either carboplatin, cisplatin, 5'DFUR, docetaxel, epirubicin, fluvastatin, gemcitabine, imatinib, paclitaxel, trastuzumab, or vinorelbine was studied in a 72-hour in vitro system using defined human cancer cell lines grown as a monolayer in exponential phase. Drug effect on growth was measured by a standard MTT assay. Median effect isobologram analysis was applied to the results to determine the presence of synergism, additive effects, or antagonism of drug combinations. Synergistic combinations were also assayed by a cytoplasmic histone-associated DNA fragmentation apoptosis assay to verify that the effect was not cytostatic. Zoledronic acid with gemcitabine demonstrated global cytotoxic synergy across 7 of 8 cell lines. Clinically achievable concentrations of fluvastatin with zoledronic acid also demonstrated synergy in 7 of 8 cell lines. All the breast cancer cell lines were sensitive. Zoledronic acid and epirubicin were antagonistic in all 4 breast cell lines studied...Continue Reading

References

Apr 26, 2000·British Journal of Cancer·S G SenaratneK W Colston
Aug 10, 2000·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·F P CoxonM J Rogers
Dec 7, 2000·Cancer Investigation·D R BudmanW Kreis
Jan 5, 2001·Expert Opinion on Investigational Drugs·G R Mundy
Apr 20, 2001·Seminars in Hematology·J R Berenson
Mar 7, 2002·Breast Cancer Research : BCR·Herbert Fleisch
Mar 15, 2002·Seminars in Oncology·Rebecca S Finley
May 16, 2002·Journal of Mammary Gland Biology and Neoplasia·J J Body
Aug 2, 2002·Breast Cancer Research and Treatment·Daniel R Budman, Anthony Calabro
Aug 10, 2002·Seminars in Oncology·Bruce D Cheson
Nov 5, 2002·Journal of Clinical Pharmacology·Tianling ChenAndrej Skerjanec
Jan 28, 2003·Cancer·Jonathan R Green
Feb 11, 2003·American Journal of Clinical Oncology·Lois M WittersAllan Lipton
Feb 14, 2003·Seminars in Oncology·James R Berenson
Feb 14, 2003·Seminars in Oncology·Robert E Coleman
Feb 20, 2003·Current Rheumatology Reports·Alfred A Reszka, Gideon A Rodan
Sep 25, 2003·Annals of Oncology : Official Journal of the European Society for Medical Oncology·D SantiniG Tonini
Oct 7, 2003·Palliative Medicine·H l Neville-Webbe, R E Coleman
Oct 8, 2003·Current Pharmaceutical Design·Michael J Rogers
Mar 23, 2004·Current Medicinal Chemistry. Anti-cancer Agents·Patrizia RussoAndrea Ardizzoni
Nov 9, 2004·Cancer Treatment Reviews·Matthijs R GraafHenk-Jan Guchelaar
Dec 2, 2004·Journal of the National Cancer Institute·Xiangguo LiuShi-Yong Sun
Mar 25, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Angela J ManthaJim Dimitroulakos

❮ Previous
Next ❯

Citations

Feb 5, 2009·Nature Clinical Practice. Oncology·Luis Costa, Pierre P Major
Jun 23, 2007·Nature Reviews. Drug Discovery·Panagiotis A KonstantinopoulosAthanasios G Papavassiliou
Sep 3, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Paul OkunieffLaurence H Baker
Mar 12, 2011·Molecular Cancer Therapeutics·Ingrid EspinozaRuth Lupu
Mar 23, 2011·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·Joaquim Bosch-BarreraCatherine Van Poznak
Nov 19, 2013·Current Problems in Cancer·Joseph FinneyMarta Batus
Apr 30, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Kathryn M CamachoSamir Mitragotri
Aug 19, 2007·Cancer Letters·Verena StresingPhilippe Clézardin
Dec 8, 2006·Trends in Pharmacological Sciences·Panagiotis A Konstantinopoulos, Athanasios G Papavassiliou
Nov 9, 2007·The Breast : Official Journal of the European Society of Mastology·R Coleman
May 8, 2007·Expert Opinion on Drug Safety·Allan Lipton
Aug 27, 2013·Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer·Roger von MoosKaren Chung
Nov 4, 2011·Clinical Pharmacology and Therapeutics·A J WiemerR J Hohl
May 13, 2014·Current Urology Reports·Neal Shore
Oct 23, 2018·Molecular and Clinical Oncology·Atsushi MitsuhashiYukio Hosomi
Dec 1, 2009·Analytical Methods : Advancing Methods and Applications·Ibrahim Ali DarwishHamoud Abdul-Mohsin Al-Malaq
Aug 16, 2017·Scientific Reports·Marwan Ibrahim AbdullahAlan Richardson
Oct 26, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Anke J RoelofsMichael J Rogers
Dec 23, 2019·RSC Medicinal Chemistry·Pimyupa ManaswiyoungkulPatrick T Gunning

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.