Ann-Marie Meredith1, Crispin R Dass1,2. 1. School of Pharmacy, Curtin University, Bentley, WA, Australia. 2. Curtin Biosciences Research Precinct, Bentley, WA, Australia.
Abstract
OBJECTIVES: The use of doxorubicin, a drug utilised for many years to treat a wide variety of cancers, has long been limited due to the significant toxicity that can occur not only during, but also years after treatment. It has multiple mechanisms of action including the intercalation of DNA, inhibition of topoisomerase II and the production of free radicals. We review the literature, with the aim of highlighting the role of drug concentration being an important determinant on the unfolding cell biological events that lead to cell stasis or death. METHODS: The PubMed database was consulted to compile this review. KEY FINDINGS: It has been found that the various mechanisms of action at the disposal of doxorubicin culminate in either cell death or cell growth arrest through various cell biological events, such as apoptosis, autophagy, senescence and necrosis. Which of these events is the eventual cause of cell death or growth arrest appears to vary depending on factors such as the patient, cell and cancer type, doxorubicin concentration and the duration of treatment. CONCLUSIONS: Further understanding of doxorubicin's influence on cell biological events could lead to an improvement in the drug's efficacy and reduce toxicity.
OBJECTIVES: The use of doxorubicin, a drug utilised for many years to treat a wide variety of cancers, has long been limited due to the significant toxicity that can occur not only during, but also years after treatment. It has multiple mechanisms of action including the intercalation of DNA, inhibition of topoisomerase II and the production of free radicals. We review the literature, with the aim of highlighting the role of drug concentration being an important determinant on the unfolding cell biological events that lead to cell stasis or death. METHODS: The PubMed database was consulted to compile this review. KEY FINDINGS: It has been found that the various mechanisms of action at the disposal of doxorubicin culminate in either cell death or cell growth arrest through various cell biological events, such as apoptosis, autophagy, senescence and necrosis. Which of these events is the eventual cause of cell death or growth arrest appears to vary depending on factors such as the patient, cell and cancer type, doxorubicin concentration and the duration of treatment. CONCLUSIONS: Further understanding of doxorubicin's influence on cell biological events could lead to an improvement in the drug's efficacy and reduce toxicity.
Authors: Aikaterini F Giannopoulou; Athanassios D Velentzas; Athanasios K Anagnostopoulos; Adamantia Agalou; Nikos C Papandreou; Stamatia A Katarachia; Dimitra G Koumoundourou; Eumorphia G Konstantakou; Vasiliki I Pantazopoulou; Anastasios Delis; Maria T Michailidi; Dimitrios Valakos; Dimitris Chatzopoulos; Popi Syntichaki; Vassiliki A Iconomidou; Ourania E Tsitsilonis; Issidora S Papassideri; Gerassimos E Voutsinas; Polydefkis Hatzopoulos; Dimitris Thanos; Dimitris Beis; Ema Anastasiadou; George Th Tsangaris; Dimitrios J Stravopodis Journal: Cancers (Basel) Date: 2021-04-22 Impact factor: 6.639