Possibilities to increase the effectiveness of doxorubicin in cancer cells killing

Abstract

Anthracycline antibiotic doxorubicin (DOX) belongs among the most important antineoplastics used in cancer therapy. Unfortunately, its cytostatic effect in therapeutic doses is frequently insufficient; but the use of higher DOX doses is limited by the development of systemic toxicity, especially cardiotoxicity. Therefore, a searching for some possibilities of how to increase DOX efficacy in cancer cells, and minimizing associated toxicities to noncancerous tissues, is in the forefront of scientific research. Many approaches are based on altered DOX metabolism. The classical strategies include an enhancing of DOX uptake by cancer cells and/or an activation of DOX prodrug within cancer cells via liposomal encapsulation or conjugation with antibodies, peptides, or synthetic polymers. The diminishing of DOX deactivation, restriction of DOX efflux from cancer cells, decreased antioxidant defense of cancer cells, changes in cell cycle, or modulation of signaling pathways represent newer approaches in increasing DOX toxicity in tumors. Each way has certain advantages and limitations. The aim of this review was not to collect all reported results, but to bring an overview of various approaches and a summary of their principles. Possible advantages, disadvantages, and further perspectives are discussed and evaluated.

Effect of selected catechins on doxorubicin antiproliferative efficacy and hepatotoxicity in vitro

“…Moreover, catechins are able to inhibit carbonyl reductase 1, the main DOX deactivation enzyme (21), and in this way they enhanced DOX efficacy in tumor-bearing mice (22). On the other hand, antioxidant properties of catechins could decrease DOX--mediated oxidative stress in cancer cells, which is believed to contribute to DOX antiproliferative effect (8,12). Owing to this fact, the risk of the possible decrease of DOX anticancer efficacy by catechins should be also kept in mind.…”

“…Many studies have focused on natural antioxidant compounds, like polyphenols (reviewed, e.g., in refs. 11,12). On the other hand, antioxidants might also reduce ROS created by cytostatics in cancer cells, and thereby interfere with the drug's antineoplastic activity (13,14).…”

Tunicamycin Potentiates Cisplatin Anticancer Efficacy through the DPAGT1/Akt/ABCG2 Pathway in Mouse Xenograft Models of Human Hepatocellular Carcinoma

“…4A and B). Several drugs have been reported to influence ABCG2 activity or expression in vitro; however, few of these drugs have been verified in animal experiments (29). Therefore, we investigated the therapeutic effect of tunicamycin in 2 hepatocellular carcinoma nude mouse models using MHCC-97L and Huh7 cells.…”

Preparation of folic acid-conjugated, doxorubicin-loaded, magnetic bovine serum albumin nanospheres and their antitumor effects in vitro and in vivo

“…3 However, its use has been limited by concomitant dose-related and irreversible cardiotoxicity, as well as the emergence of drug resistance. 4 Damage to nontargeted tissues often stymies cancer therapy by limiting the doxorubicin dosage. 5 The underlying causes of drug resistance remain unknown, so it is important to establish delivery systems to minimize doxorubicin-induced toxicity while obtaining maximum anticancer efficacy.…”