Gallic acid-loaded chitosan nanoparticles enhance the DNA damage and apoptotic features through inhibiting flap endonuclease-1 in triple-negative breast cancer cells

Monica Velaiyan; Rajasekar Muthusamy; Miguel Kativa; Asaikkutti Annamalai; Annamalai Govindhan; Parthipan Punniyakotti; Agilan Balupillai

doi:10.1002/tox.24293

Gallic acid-loaded chitosan nanoparticles enhance the DNA damage and apoptotic features through inhibiting flap endonuclease-1 in triple-negative breast cancer cells

Environ Toxicol. 2024 Apr 26. doi: 10.1002/tox.24293. Online ahead of print.

Authors

Monica Velaiyan¹, Rajasekar Muthusamy², Miguel Kativa¹, Asaikkutti Annamalai¹, Annamalai Govindhan³, Parthipan Punniyakotti⁴, Agilan Balupillai¹

Affiliations

¹ Department of Biotechnology, School of Life Sciences, Pondicherry University, Puducherry, India.
² Central Research Laboratory, Vinayaka Mission's Kirupananda Variyar Medical College and Hospitals, Salem, Tamil Nadu, India.
³ Department of Medicine, Immunology, Allergy and Rheumatology, Baylor College of Medicine, Houston, Texas, USA.
⁴ Department of Biotechnology, Faculty of Science and Humanities, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India.

PMID: 38666519
DOI: 10.1002/tox.24293

Abstract

This study investigated the fabrication of gallic acid-loaded chitosan nanoparticles (Gal-Chi-NPs) that enhanced the DNA damage and apoptotic features by inhibiting FEN-1 expressions in MDA-MB 231 cells. Gal-Chi-NPs were fabricated by the ionic gelation method, and it was characterized by several studies such as dynamic light spectroscopy, Fourier-transforms infrared spectroscopy, x-ray diffraction, scanning electron microscopy, energy-dispersive x-ray, atomic force microscopy, and thermogravimetric analysis. We have obtained that Gal-Chi-NPs displayed 182.2 nm with crystal, smooth surface, and heat stability in nature. Gal-Chi-NPs induce significant toxicity in MDA-MB-231 cells that compared with normal NIH-3T3 cells. A significant reactive oxygen species (ROS) overproduction was observed in Gal-Chi-NPs treated MDA-MB-231. Flap endonuclease-1 (FEN-1) is a crucial protein involved in long patch base excision repair that is involved in repairing the chemotherapeutic mediated DNA-damaged base. Therefore, inhibition of FEN-1 protein expression is a crucial target for enhancing chemotherapeutical efficacy. In this study, we have obtained that Gal-Chi-NPs treatment enhanced the DNA damage by observing increased p-H2AX, PARP1; and suppressed the expression of FEN-1 in MDA-MB-231 cells. Moreover, Gal-Chi-NPs inhibited the expression of tumor proliferating markers p-PI3K, AKT, cyclin-D1, PCNA, and BCL-2; induced proapoptotic proteins (Bax and caspase-3) in MDA-MB 231 cells. Thus, Gal-Chi-NPs induce DNA damage and apoptotic features and inhibit tumor proliferation by suppressing FEN-1 expression in triple-negative breast cancer cells.

Keywords: chitosan; flap endonuclease‐1; gallic acid; triple‐negative breast cancer.