Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Feb;104(2):97-109.
doi: 10.1111/ejh.13347. Epub 2019 Dec 19.

An artificial nucleoside that simultaneously detects and combats drug resistance to doxorubicin

Jung-Suk Choi  1 , Anthony Berdis  1   2
Affiliations

An artificial nucleoside that simultaneously detects and combats drug resistance to doxorubicin

Jung-Suk Choi et al. Eur J Haematol. 2020 Feb.

Abstract

Objectives: Doxorubicin is a DNA-damaging agent used to treat hematological cancers. Unfortunately, drug resistance can occur by defective DNA repair activity coupled with the ability of DNA polymerases to misreplicate unrepaired DNA lesions. This study demonstrates that the efficacy of doxorubicin can be improved by using an artificial nucleoside to efficiently and selectively inhibit this activity.

Methods: In vitro studies using acute lymphoblastic leukemia cell lines define the mechanism of cell death caused by combining an artificial nucleoside with doxorubicin.

Results: Flow cytometry experiments demonstrate that combining an artificial nucleoside with doxorubicin potentiates the cell killing effects of the drug by increasing apoptosis. The potentiation effect correlates with expression of TdT, a specialized DNA polymerase overexpressed in acute lymphoblastic leukemia. Cell cycle experiments demonstrate that this combination blocks cells at S-phase prior to inducing apoptosis. Finally, the unique chemical composition of the nucleoside analog was used to visualize the replication of damaged DNA in TdT-positive cells. This represents a potential diagnostic tool to easily identify doxorubicin-resistant cancer cells.

Conclusion: Studies demonstrate that a novel artificial nucleoside improves the therapeutic efficacy of doxorubicin, thereby reducing the risk of potential side effects caused by the DNA-damaging agent.

Keywords: DNA damage; DNA polymerization; chemotherapy; nucleoside analogs.

PubMed Disclaimer

References

REFERENCES

    1. Mao Z, Shen K, Zhu L, et al. Comparisons of cardiotoxicity and efficacy of anthracycline-based therapies in breast cancer: A network meta-analysis of randomized clinical trials. Oncol Res Treat. 2019;17:1-9.
    1. Pignata S, C Cecere S, Du Bois A, Harter P, Heitz F. Treatment of recurrent ovarian cancer. Ann Oncol. 2017;28(suppl_8):viii51-viii56.
    1. Waqar SN, Morgensztern D. Treatment advances in small cell lung cancer (SCLC). Pharmacol Ther. 2017;180:16-23.
    1. Pendleton M, Lindsey RH Jr, Felix CA, Grimwade D, Osheroff N. Topoisomerase II and leukemia. Ann NY Acad Sci. 2014;1310:98-110.
    1. Songbo M, Lang H, Xinyong C, Bin X, Ping Z, Liang S. Oxidative stress injury in doxorubicin-induced cardiotoxicity. Toxicol Lett. 2019;307:41-48.

MeSH terms

LinkOut - more resources