Doxorubicin: Insights into Dynamics, Clinical Uses and Adverse Effects

Amal A. Alghorabi¹, Ahmed M. Kabel^{2, 3,} and Maaly A. Abd Elmaaboud²

¹Pharm D, College of Pharmacy, Taif University, Taif, Saudi Arabia

²Pharmacology Department, Faculty of Medicine, Tanta University, Tanta, Egypt

³Department of Clinical Pharmacy, College of Pharmacy, Taif University, Taif, Saudi Arabia

Cite this paper:
Amal A. Alghorabi, Ahmed M. Kabel and Maaly A. Abd Elmaaboud. Doxorubicin: Insights into Dynamics, Clinical Uses and Adverse Effects. Journal of Cancer Research and Treatment. 2019; 7(1):17-20. doi: 10.12691/jcrt-7-1-3

Abstract

Doxorubicin (DOX) is one of the anthracycline antibiotics that is used frequently for treatment of various types of malignancies including lung, breast and testicular cancers. DOX reacts with DNA by intercalation and inhibits the synthesis of DNA macromolecular components. Also, it may increase the production of free radicals which may contribute to its cytotoxicity. DOX may cause serious adverse effects including cardiotoxicity, hepatotoxicity and testicular toxicity. So, it has become increasingly important to find pharmacological remedies to protect against these serious adverse effects. This mini-review sheds light on DOX including its history, dynamics, clinical uses and adverse effects.

Keywords:
doxorubicin dynamics uses toxicity

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References:

[1]	Kabel AM. Zinc/alogliptin combination attenuates testicular toxicity induced by doxorubicin in rats: Role of oxidative stress, apoptosis and TGF-β1/NF-κB signaling. Biomed Pharmacother 2018; 97: 439-49.
[2]	Yang F, Teves SS, Kemp CJ, Henikoff S. Doxorubicin, DNA torsion, and chromatin dynamics. Biochim Biophys Acta 2014; 1845(1): 84-9.
[3]	Denard B, Lee C, Ye J. Doxorubicin blocks proliferation of cancer cells through proteolytic activation of CREB3L1. Elife 2012; 1:e00090.
[4]	Mansouri E, Jangaran A, Ashtari A. Protective effect of pravastatin on doxorubicin-induced hepatotoxicity. Bratisl Lek Listy 2017; 118(5): 273-7.
[5]	Nagai K, Fukuno S, Oda A, Konishi H. Protective effects of taurine on doxorubicin-induced acute hepatotoxicity through suppression of oxidative stress and apoptotic responses. Anticancer Drugs 2016; 27(1): 17-23.
[6]	Ye XL, Huang WC, Zheng YT, Liang Y, Gong WQ, Yang CM, Liu B. Irbesartan ameliorates cardiac inflammation in type 2 diabetic db/db mice. Nan Fang Yi Ke Da XueXueBao 2016; 37(4): 505-11.
[7]	Yaguchi S, Ogawa Y, Shimmura S, et al. Angiotensin II Type 1 Receptor Antagonist Attenuates Lacrimal Gland, Lung, and Liver Fibrosis in a Murine Model of Chronic Graft-Versus-Host Disease. Yang P-C, ed. PLoS One 2013; 8(6): e64724.
[8]	Tacar O, Sriamornsak P, Dass CR. Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems. Journal of Pharmacy and Pharmacology 2013; 65 (2): 157-70.
[9]	Weiss RB. The anthracyclines: will we ever find a better doxorubicin?. Seminars in Oncology 1992; 19 (6): 670-86.
[10]	Di Marco A, Gaetani M, Scarpinato B. Adriamycin (NSC-123, 127): a new antibiotic with antitumor activity. Cancer Chemother Rep 1969; 53 (1): 33-7.
[11]	Hynek D, Krejcova L, Zitka O, Adam V, Trnkova L, Sochor J, et al.Electrochemical Study of Doxorubicin Interaction with Different Sequences of Single Stranded Oligonucleotides, Part I. Int J Electrochem Sci 2012; 7: 13-33.
[12]	Barpe DR, Rosa DD, Froehlich PE. Pharmacokinetic evaluation of doxorubicin plasma levels in normal and overweight patients with breast cancer and simulation of dose adjustment by different indexes of body mass. Eur J Pharm Sci 2010; 41(3-4): 458-63.
[13]	Pommier Y, Leo E, Zhang H, Marchand C.DNA topoisomerases and their poisoning by anticancer and antibacterial drugs. Chemistry & Biology 2010; 17 (5): 421-33.
[14]	Pang B, Qiao X, Janssen L, Velds A, Groothuis T, Kerkhoven R, et al. Drug-induced histone eviction from open chromatin contributes to the chemotherapeutic effects of doxorubicin. Nature Communications 2013; 4 (5): 1908.
[15]	Friedman R, Caflisch A. Discovery of Plasmepsin Inhibitors by Fragment-Based Docking and Consensus Scoring. Chem Med Chem 2009; 4 (8): 1317-26.
[16]	Al-Harthi SE, Alarabi OM, Ramadan WS, Alaama MN, Al-Kreathy HM, Damanhouri ZA, et al. Amelioration of doxorubicin induced cardiotoxicity by resveratrol. Mol Med Rep 2014; 10: 1455-60.
[17]	Shi Y, Moon M, Dawood S, McManus B, Liu PP. Mechanisms and management of doxorubicin cardiotoxicity. Herz 2011; 36: 296-305.
[18]	Kaczmarek A, Brinkman BM, Heyndrickx L, Vandenabeele P, Krysko DV. Severity of doxorubicin-induced small intestinal mucositis is regulated by the TLR-2 and TLR-9 pathway. J Pathol 2012; 226 (4): 598-608.
[19]	Dillon R, Hirschfield GM, Allison ME, Rege KP. Fatal reactivation of hepatitis B after chemotherapy for lymphoma. BMJ 2008; 337: a423.
[20]	Cappetta D, De Angelis A, Sapio L, et al. Oxidative Stress and Cellular Response to Doxorubicin: A Common Factor in the Complex Milieu of Anthracycline Cardiotoxicity. Oxid Med Cell Longev. 2017; 2017: 1521020.
[21]	Octavia Y, Tocchetti CG, Gabrielson KL, Janssens S, Crijns HJ, Moens AL. Doxorubicin-induced cardiomyopathy: from molecular mechanisms to therapeutic strategies. J Mol Cell Cardiol 2012; 52(6): 1213-25.
[22]	Volkova M, Russell R 3rd. Anthracycline cardiotoxicity: prevalence, pathogenesis and treatment. Curr Cardiol Rev 2011; 7(4): 214-20.
[23]	Polegato BF, Minicucci MF, Azevedo PS, Carvalho RF, Chiuso-Minicucci F, Pereira EJ, Paiva SA, Zornoff LA, Okoshi MP, Matsubara BB, Matsubara LS. Acute doxorubicin-induced cardiotoxicity is associated with matrix metalloproteinase-2 alterations in rats. Cell Physiol Biochem 2015; 35(5): 1924-33.
[24]	Kabel AM, Elkhoely AA. Targeting proinflammatory cytokines, oxidative stress, TGF-β1 and STAT-3 by rosuvastatin and ubiquinone to ameliorate trastuzumab cardiotoxicity. Biomed Pharmacother 2017; 93: 17-26.
[25]	Singla S, Kumar NR, Kaur J. In vivo Studies on the Protective Effect of Propolis on Doxorubicin-Induced Toxicity in Liver of Male Rats. Toxicol Int 2014; 21(2):191-5.
[26]	Gao Y, Yang H, Fan Y, Li L, Fang J, Yang W. Hydrogen-Rich Saline Attenuates Cardiac and Hepatic Injury in Doxorubicin Rat Model by Inhibiting Inflammation and Apoptosis. Mediators Inflamm 2016; 2016:1320365.
[27]	Dent P. The flip side of doxorubicin: Inflammatory and tumor promoting cytokines. Cancer Biol Ther 2013; 14(9): 774-5.