Characterization of Caerulomycin A as a dual-targeting anticancer agent

Lingying Tong; Weichao Sun; Shiyong Wu; Yong Han

doi:10.1016/j.ejphar.2022.174914

Characterization of Caerulomycin A as a dual-targeting anticancer agent

Eur J Pharmacol. 2022 May 5:922:174914. doi: 10.1016/j.ejphar.2022.174914. Epub 2022 Mar 23.

Authors

Lingying Tong¹, Weichao Sun², Shiyong Wu³, Yong Han⁴

Affiliations

¹ Edison Biotechnology Institute, Ohio University, Athens, OH, 45701, USA; Department of Chemistry and Biochemistry, Ohio University, Athens, OH, 45701, USA.
² Edison Biotechnology Institute, Ohio University, Athens, OH, 45701, USA.
³ Edison Biotechnology Institute, Ohio University, Athens, OH, 45701, USA; Department of Chemistry and Biochemistry, Ohio University, Athens, OH, 45701, USA; Molecular and Cellular Biology Program, Ohio University, Athens, OH, 45701, USA.
⁴ Edison Biotechnology Institute, Ohio University, Athens, OH, 45701, USA. Electronic address: hany@ohio.edu.

Abstract

Caerulomycin A (CaeA), isolated from actinomycetes, has a featured 2,2'-bipyridine core structure. Based on the results of in silico drug-protein docking analysis, CaeA shows potential ligands for interacting with both tubulin and DNA topoisomerase I (Topo-1). The result was confirmed by cell-free tubulin polymerization assay and Topo-1 activity assay. In vitro assays also demonstrated that CaeA increases the polymerization of tubulin and increases cell size. In addition, CaeA inhibits cell viability and growth of various cancer cells, yet exhibits low cytotoxicity. CaeA also affects paclitaxel-resistant cancer cells and synergizes the effect with paclitaxel in reducing cancer cell colony formation rate. In vivo experiments confirm the effect of CaeA on reducing tumor size and weight in nude mouse inoculated with tumor cells with no noticeable side effects. Taken together, our data demonstrate that CaeA is a potential potent agent for cancer treatment through tubulin and Topo-1 dual-targeting with little side effects.

Keywords: Caerulomycin A; Dual-targeting anticancer agent; Topoisomerase I; Tubulin.

MeSH terms

2,2'-Dipyridyl / pharmacology
2,2'-Dipyridyl / therapeutic use
Animals
Antineoplastic Agents* / therapeutic use
Cell Line, Tumor
Cell Proliferation
Drug Screening Assays, Antitumor
Mice
Neoplasms* / drug therapy
Paclitaxel / pharmacology
Pyridines
Tubulin

Substances

Antineoplastic Agents
Pyridines
Tubulin
caerulomycin A
2,2'-Dipyridyl
Paclitaxel

Grants and funding

R01 ES030425/ES/NIEHS NIH HHS/United States