Enhancement of cytotoxicity of artemisinins toward cancer cells by ferrous iron

Free Radical Biology & Medicine
Thomas EfferthManfred Marschall

Abstract

Iron(II) heme-mediated activation of the peroxide bond of artemisinins is thought to generate the radical oxygen species responsible for their antimalarial activity. We analyzed the role of ferrous iron in the cytotoxicity of artemisinins toward tumor cells. Iron(II)-glycine sulfate (Ferrosanol) and transferrin increased the cytotoxicity of free artesunate, artesunate microencapsulated in maltosyl-beta-cyclodextrin, and artemisinin toward CCRF-CEM leukemia and U373 astrocytoma cells 1.5- to 10.3-fold compared with that of artemisinins applied without iron. Growth inhibition by artesunate and ferrous iron correlated with induction of apoptosis. Cell cycle perturbations by artesunate and ferrous iron were not observed. Treatment of p53 wild-type TK6 and p53 mutated WTK1 lymphoblastic cells showed that mutational status of the tumor suppressor p53 did not influence sensitivity to artesunate. The effect of ferrous iron and transferrin was reversed by monoclonal antibody RVS10 against the transferrin receptor (TfR), which competes with transferrin for binding to TfR. CCRF-CEM and U373 cells expressed TfR in 95 and 48% of the cell population, respectively, whereas TfR expression in peripheral mononuclear blood cells of four healthy d...Continue Reading

References

Jan 1, 1991·Pathobiology : Journal of Immunopathology, Molecular and Cellular Biology·N ShtermanC Moroz
Jul 1, 1990·Statistics in Medicine·Y Hochberg, Y Benjamini
Sep 1, 1980·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·E AulbertD Gericke
May 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·I S Trowbridge, M B Omary
Jul 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·R SutherlandM Greaves
May 1, 1983·Journal of Clinical Pathology·K C GatterD Y Mason
Nov 1, 1980·The Journal of Experimental Medicine·W JuddJ L Strominger
Apr 1, 1995·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·F Nosten, R N Price
Jun 1, 1993·Journal of Natural Products·H J WoerdenbagA W Konings
Apr 9, 1999·Cancer Gene Therapy·B BadieD A Boothman
Mar 4, 2000·Nature Genetics·U ScherfJ N Weinstein
Mar 30, 2002·Critical Reviews in Oncology/hematology·Juliana C Kwok, Des R Richardson
Apr 27, 2002·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Thomas EfferthEng-Shang Huang
May 30, 2002·The British Journal of Mathematical and Statistical Psychology·H J KeselmanBurt Holland
Oct 25, 2002·Redox Report : Communications in Free Radical Research·Shinya Toyokuni
Jul 19, 2003·Molecular Pharmacology·Thomas EfferthJens Oliver Funk

❮ Previous
Next ❯

Citations

Jul 5, 2007·Cancer Chemotherapy and Pharmacology·Deguang MuFaguang Jin
Mar 22, 2012·Apoptosis : an International Journal on Programmed Cell Death·Fenglian XiaoTongsheng Chen
Sep 1, 2012·Investigational New Drugs·Henry C LaiTomikazu Sasaki
Nov 14, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Shokoofe Noori, Zuhair M Hassan
May 10, 2005·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Thomas Efferth
Feb 15, 2005·Drug Discovery Today·Peter T GommeJoseph Bertolini
Nov 4, 2009·Expert Reviews in Molecular Medicine·Gary L Firestone, Shyam N Sundar
Sep 12, 2009·Anti-cancer Drugs·Marcel RamacherThomas Efferth
Feb 5, 2010·Anti-cancer Drugs·Colm MorrisseyTomikazu Sasaki
Dec 17, 2011·Journal of Biomedicine & Biotechnology·Maria P Crespo-Ortiz, Ming Q Wei
Jul 13, 2012·BMC Complementary and Alternative Medicine·Chuan Bian LimYan Zhao
Jun 8, 2011·Radiation Oncology·Thomas Efferth, Peter Langguth
Jul 6, 2007·Chinese Medicine·Rolf RauhThomas Efferth
Jul 23, 2011·Chinese Medicine·Wen TanYitao Wang
Aug 2, 2011·Chemical & Pharmaceutical Bulletin·Lijun XieYanfang Zhao
Jan 7, 2014·PloS One·Rob Hooft van HuijsduijnenTimothy N C Wells
Apr 3, 2008·American Journal of Veterinary Research·Kenji HosoyaWilliam C Kisseberth
Feb 5, 2008·Zhong xi yi jie he xue bao = Journal of Chinese integrative medicine·Zhu-Yi ZhangDan-Qi Li
Sep 26, 2013·The Journal of Veterinary Medical Science·Seishiro ChikazawaSeiichi Higuchi
Oct 23, 2013·Proceedings of the National Academy of Sciences of the United States of America·Edgar DeuMatthew Bogyo
Jun 3, 2014·Daru : Journal of Faculty of Pharmacy, Tehran University of Medical Sciences·Amir GharibRamin Saravani
Dec 10, 2013·Pharmacology & Therapeutics·Wanxing Eugene HoW S Fred Wong
Oct 25, 2012·Expert Opinion on Investigational Drugs·Min HuangYi-Tao Wang
Jul 1, 2014·IUBMB Life·Sourajit Soumyaranjan DasDebasmita Pankaj Alone
May 27, 2014·Natural Products and Bioprospecting·Elmar Breuer, Thomas Efferth
Feb 11, 2010·Chemico-biological Interactions·Serkan SertelThomas Efferth
Mar 3, 2009·Bioorganic & Medicinal Chemistry Letters·Michael JonesPaul M O'Neill
May 13, 2008·Nitric Oxide : Biology and Chemistry·V Badireenath KonkimallaThomas Efferth
Dec 15, 2015·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Friedrich-Wilhelm MichaelsenThomas Efferth

❮ 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.

Antimalarial Agents (ASM)

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.

Cancer Metabolism

In order for cancer cells to maintain rapid, uncontrolled cell proliferation, they must acquire a source of energy. Cancer cells acquire metabolic energy from their surrounding environment and utilize the host cell nutrients to do so. Here is the latest research on cancer metabolism.

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.

Antimalarial Agents

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.