Online citations, reference lists, and bibliographies.
Please confirm you are human
(Sign Up for free to never see this)
← Back to Search

Hydrogen Peroxide Overproduced In Breast Cancer Cells Can Serve As An Anticancer Prodrug Generating Apoptosis‐stimulating Hydroxyl Radicals Under The Effect Of Tamoxifen‐ferrocene Conjugate

W. A. Wlassoff, C. Albright, Michael S Sivashinski, A. Ivanova, Jacob Appelbaum, Rudolph I Salganik
Published 2007 · Chemistry, Medicine

Save to my Library
Download PDF
Analyze on Scholarcy
Share
A new approach to the treatment of cancer is suggested, based on the innate overproduction of hydrogen peroxide in cancer cells. Hydrogen peroxide serves as a prodrug in the presence of transition metal ions, such as iron delivered by ferrocene. Under the effect of ferrocene, hydrogen peroxide is split into hydroxyl anions and highly reactive hydroxyl radicals. The latter cause oxidative DNA damage, which induces apoptosis, leading to elimination of cancer cells. Tamoxifen, a drug that interacts with oestrogen receptors, was used as a carrier to deliver ferrocene to breast cancer cells. For this aim tamoxifen conjugated to ferrocene (Tam‐Fer) was synthesized. We have shown that the frequency of apoptotic events in MCF‐7 breast cancer cells treated with Tam‐Fer is significantly higher than in cells treated with tamoxifen or ferrocene separately. The increase of apoptosis correlates well with the rise in generation of reactive oxygen species in cancer cells. These results show that the hydrogen peroxide overproduced in tumour cells can serve as a prodrug for the treatment of cancer.
This paper references
Direct detection of 8 - oxodeoxyguanine by avidin and its analogue
T. P. Szatrowski (1991)
Apoptosis , its significance in cancer therapy
P. Köpf-Maier (1984)
10.1039/CC9960000955
Ferrocenyl hydroxytamoxifen: a prototype for a new range of oestradiol receptor site-directed cytotoxics
S. Top (1996)
10.1016/S0022-328X(01)00953-6
Studies on organometallic selective estrogen receptor modulators. (SERMs) Dual activity in the hydroxy-ferrocifen series
S. Top (2001)
Antioxidant enzyme levels in cancer.
Oberley Td (1997)
10.1016/0014-5793(94)01368-B
Persistent oxidative stress in cancer
S. Toyokuni (1995)
Choline depletion induces apoptosis in SV 40 - immortalized CWSV - 1 rat hepatocytes in culture
C. D. Albright (1995)
10.1177/41.1.7678025
A new method to detect apoptosis in paraffin sections: in situ end-labeling of fragmented DNA.
J. Wijsman (1993)
10.1096/fasebj.10.4.8647350
Choline deficiency induces apoptosis in SV40‐immortalized CWSV‐1 rat hepatocytes in culture 1
C. Albright (1996)
10.1021/JA00811A029
Organophosphinepalladium complexes as catalysts for vinylic hydrogen substitution reactions
H. A. Dieck (1974)
Antitumor enzyme level in cancer
K. Okamoto (1996)
10.1002/1097-0142(19940415)73:8<2013::AID-CNCR2820730802>3.0.CO;2-J
Apoptosis. Its significance in cancer and cancer Therapy
J. Kerr (1994)
Tumor - activated prodrug – a new approach to cancer therapy
W. Denny (2004)
10.1002/ANIE.198404561
Ferrocenium Salts—The First Antineoplastic Iron Compounds
Priv.-Doz. Dr. Petra Köpf-Maier (1984)
A new method to detect apoptosis in paraffin sections: in situ end-labeling of fragment DNA
J H Wijsman (1993)
10.1080/07315724.2001.10719185
The Benefits and Hazards of Antioxidants: Controlling Apoptosis and Other Protective Mechanisms in Cancer Patients and the Human Population
R. Salganik (2001)
10.1006/ABIO.1997.2354
Direct detection of 8-oxodeoxyguanosine and 8-oxoguanine by avidin and its analogues.
L. Struthers (1998)
10.1093/embo-reports/kvf094
ROS, stress‐activated kinases and stress signaling in cancer
M. Benhar (2002)
10.1081/CNV-200027148
Tumor-activated Prodrugs—A New Approach to Cancer Therapy
W. Denny (2004)
10.1007/BF01247464
Antioxidant enzyme activities and oxidative stress in human breast cancer
K. Punnonen (2005)
10.1016/0891-5849(94)00198-S
Superoxide and hydrogen peroxide in relation to mammalian cell proliferation.
R. Burdon (1995)
10.1093/CARCIN/21.5.909
Dietary antioxidant depletion: enhancement of tumor apoptosis and inhibition of brain tumor growth in transgenic mice.
R. Salganik (2000)
10.1002/cncr.10593
Annual Report to the Nation on the status of cancer, 1973–1999, featuring implications of age and aging on U.S. cancer burden
B. Edwards (2002)
10.1002/(SICI)1097-0215(19960208)65:4<437::AID-IJC7>3.0.CO;2-Y
Overexpression of human mutT homologue gene messenger RNA in renal‐cell carcinoma: Evidence of persistent oxidative stress in cancer
K. Okamoto (1996)
10.1093/JN/134.5.1139
Dietary depletion of vitamin E and vitamin A inhibits mammary tumor growth and metastasis in transgenic mice.
C. Albright (2004)
10.1093/jnci/djn389
Annual Report to the Nation on the Status of Cancer, 1975–2005, Featuring Trends in Lung Cancer, Tobacco Use, and Tobacco Control
A. Jemal (2008)
Production of large amounts of hydrogen peroxide by human tumor cells.
T. Szatrowski (1991)



This paper is referenced by
Targeting the translational machinery in aggressive cancers
Ella Lineham (2019)
10.1155/2017/3481710
Triethylenetetramine Synergizes with Pharmacologic Ascorbic Acid in Hydrogen Peroxide Mediated Selective Toxicity to Breast Cancer Cell
Lian-lian Wang (2017)
10.1039/c0cc01290d
Synthesis of cytotoxic ferrocenyl flavones via a ferricenium-mediated 1,6-oxidative cyclization.
Jean-Philippe Monserrat (2010)
10.1007/978-3-642-13185-1_4
Ferrocene Functionalized Endocrine Modulators as Anticancer Agents
E. Hillard (2010)
10.18632/oncotarget.25470
Folic acid–conjugated mesoporous silica particles as nanocarriers of natural prodrugs for cancer targeting and antioxidant action
K. AbouAitah (2018)
10.1016/J.CHEMPR.2019.05.024
Size-Tunable Assemblies Based on Ferrocene-Containing DNA Polymers for Spatially Uniform Penetration
Jie Tan (2019)
10.1016/j.jconrel.2015.11.027
Polymeric micellar nanoplatforms for Fenton reaction as a new class of antibacterial agents.
S. Park (2016)
10.1016/j.colsurfb.2014.06.024
pH and hydrogen peroxide dual responsive supramolecular prodrug system for controlled release of bioactive molecules.
Y. Wang (2014)
10.1007/s10072-014-1730-8
The ferric iron chelator 2,2′-dipyridyl attenuates basilar artery vasospasm and improves neurological function after subarachnoid hemorrhage in rabbits
Yaoyu Yu (2014)
10.17221/401/2015-CJFS
Determination of trans-resveratrol action on two different types of neuronal cells, neuroblastoma and hippocampal cells
Joanna Gerszon (2016)
10.1021/acs.biomac.8b01673
Active, Autonomous, and Adaptive Polymeric Particles for Biomedical Applications
Shauni Keller (2019)
10.1021/OM400490A
Synthesis, Characterization, and Antiproliferative Activities of Novel Ferrocenophanic Suberamides against Human Triple-Negative MDA-MB-231 and Hormone-Dependent MCF-7 Breast Cancer Cells
José de Jesús Cázares-Marinero (2013)
INDUCING OXIDATIVE STRESS USING BIOTIN-RECEPTOR TARGETED ORGANOMETALLIC COMPOUNDS ON CANCER CELLS
G. Akkaraju (2019)
10.1371/journal.pcbi.1005352
Activated Oncogenic Pathway Modifies Iron Network in Breast Epithelial Cells: A Dynamic Modeling Perspective
Julia Chifman (2017)
10.3390/molecules23092126
Probing the Anticancer Action of Novel Ferrocene Analogues of MNK Inhibitors
Supojjanee Sansook (2018)
10.3390/app10113728
The Cytotoxic Effect of Newly Synthesized Ferrocenes against Cervical Carcinoma Cells Alone and in Combination with Radiotherapy
H. Skoupilová (2020)
10.1002/anie.201712027
Simultaneous Fenton-like Ion Delivery and Glutathione Depletion by MnO2 -Based Nanoagent to Enhance Chemodynamic Therapy.
Lisen Lin (2018)
10.3164/jcbn.11-105
Literature review of the role of hydroxyl radicals in chemically-induced mutagenicity and carcinogenicity for the risk assessment of a disinfection system utilizing photolysis of hydrogen peroxide
T. Kanno (2012)
10.1002/adma.201801964
Gas-Generating Nanoplatforms: Material Chemistry, Multifunctionality, and Gas Therapy.
Luodan Yu (2018)
10.1039/C8TB03320J
Glucose oxidase and polydopamine functionalized iron oxide nanoparticles: combination of the photothermal effect and reactive oxygen species generation for dual-modality selective cancer therapy.
T. Zhang (2019)
10.1016/j.freeradbiomed.2012.06.030
Maintenance of higher H₂O₂ levels, and its mechanism of action to induce growth in breast cancer cells: important roles of bioactive catalase and PP2A.
S. Sen (2012)
10.1002/anie.201504186
Self-Guided Supramolecular Cargo-Loaded Nanomotors with Chemotactic Behavior towards Cells
Fei Peng (2015)
10.1016/J.JIEC.2019.07.004
Fenton-like reaction performing mineralized nanocarriers as oxidative stress amplifying anticancer agents
H. Kim (2019)
10.1016/J.POLY.2016.05.039
Synthesis of new ferrocenyl dehydrozingerone derivatives and their effects on viability of PC12 cells
S. Pedotti (2016)
10.1002/EJIC.201600860
Synthesis and reactivity of ferrocenyl allylamine derivatives.
E. Manoury (2016)
10.1038/S41570-017-0066
The medicinal chemistry of ferrocene and its derivatives
M. Patra (2017)
10.1021/jm2014937
Aminoferrocene-based prodrugs activated by reactive oxygen species.
Helen Hagen (2012)
10.1016/j.mtcomm.2020.101842
Construction of ferrocene modified and indocyanine green loaded multifunctional mesoporous silica nanoparticle for simultaneous chemodynamic/photothermal/photodynamic therapy
Renlu Han (2020)
10.1002/ADFM.201801783
A Versatile Pt‐Based Core–Shell Nanoplatform as a Nanofactory for Enhanced Tumor Therapy
Xiao-shuang Wang (2018)
10.1016/j.biomaterials.2019.04.023
Nanocatalysts-augmented Fenton chemical reaction for nanocatalytic tumor therapy.
Xiaoqin Qian (2019)
10.1007/s13277-016-5224-6
Oxystressed tumor microenvironment potentiates epithelial to mesenchymal transition and alters cellular bioenergetics towards cancer progression
Dhivya Sridaran (2016)
10.1002/advs.202001223
Porous Pt Nanospheres Incorporated with GOx to Enable Synergistic Oxygen‐Inductive Starvation/Electrodynamic Tumor Therapy
Zijie Lu (2020)
See more
Semantic Scholar Logo Some data provided by SemanticScholar