Curcumin induces DNA damage by mediating homologous recombination mechanism in triple negative breast cancer

Abstract

Curcumin has a therapeutic potential activity through modulation of different signaling pathways in various types of cancer. However, the relationship between the efficacy of curcumin and the homologous recombination (HR) mechanism which plays important roles in the repair of double strand DNA (dsDNA) breaks remains uncertain. Herein, we explored curcumin-dependent dsDNA breaks and the association of curcumin with HR mechanism in triple negative breast cancer (TNBC). The cytotoxic and therapeutic activity of curcumin on HCC1937 (BRCA1 mutant), MDA-MB-231 (BRCA1 wild type) TNBC and HUVEC control cell lines were assessed. Then, the expression level and subcellular localization of H2AX, PARP1, BRCA1 and RAD51 were detected by RT-PCR and immunofluorescence analysis. Furthermore, ultrastructural changes of cell death were observed by TEM. Our findings for the first time demonstrated that curcumin’s therapeutic activity was more pronounced in HCC1937 cells through the suppression of HR mechanism and the induction of dsDNA breaks. Consequently, curcumin based therapy could benefit in patients with TNBC particularly especially in women with a BRCA1 mutation.

Acknowledgment

We thank Department of Medical Biology, Uludag University for supporting our analysis.

Author’s Contributions

GGE and ADO conceived and designed research. GGE and ADO conducted experiments. ES performed immunofluorescence analysis and interpretation of ultrastructural images. OTCK performed TEM Analysis. SK analyzed data. GGE wrote the manuscript. All authors read carefully and approved the manuscript.

Disclosure Statement

The authors declare no financial interest.

Additional information

Funding

This study was supported by the Scientific Research Projects Foundation (BAP) of the Sakarya University of Turkey [Projects No: 2018-3-12-295 and 2019-5-19-62].