# Curcumin in High Doses Reverses the UV-B-Induced DNMT and HDAC Upregulation In Vitro: A Novel Anti-Cancer Approach?

## TL;DR

This study shows that high-dose curcumin can reduce UV-induced gene expression of DNMT and HDAC enzymes, which are linked to cancer development.

## Contribution

The study is the first to examine curcumin's effect on DNMT and HDAC gene expression in response to UV radiation in specific cancer and skin cells.

## Key findings

- UV exposure increased DNMT and HDAC gene expression in HaCaT, HepG2, and A549 cells.
- Curcumin reduced the mRNA levels of DNMT and HDAC genes in a dose-dependent manner in A549 and HaCaT cells.
- Curcumin also reduced UV-induced gene expression in HepG2 cells, though less significantly.

## Abstract

Background/Objectives: The primary mechanisms driving UV-induced carcinogenesis include DNA damage leading to mutations, and reactive oxygen species (ROS) formation that can cause inflammation, immunosuppression, alteration of the structure of proteins, including transcription factors, and carcinogenesis through epigenetic modifications. Curcumin has the potential to inhibit DNA-methyltransferases (DNMTs) and histone deacetylases (HDACs), but this has not been examined yet at the gene-expression level. In this article, we aimed to explore the potential protective effect of curcumin against UV radiation-induced DNMT1, DNMT3A, DNMT3B, HDAC5, and HDAC6 expression in immortalized keratinocytes (HaCaT), hepatocellular carcinoma (HepG2), and lung adenocarcinoma (A549) cells. Methods: Cells were exposed to UV-B radiation for different periods and treated with curcumin at different concentrations to evaluate dose-related trends in DNMT and HDAC gene expression compared with untreated UV-exposed cells. Results: UV exposure increased the DNMT and HDAC gene expression levels in the examined cells dose-dependently. Curcumin exposure resulted in decreased mRNA expression levels of DNMT and HDAC gene expression. In our experimental setup curcumin modulated the transcription of DNMT and HDAC genes in A549 and HaCaT cells in a dose-dependent manner. In HepG2 cells, UV-B induced a less pronounced, but still significant, increase in the examined gene expression levels. This effect was also dose-dependently decreased by curcumin, although less markedly. Conclusions: Future studies are warranted to examine if curcumin combined with other chemopreventive agents through the HDAC and DNMT inhibitory activity at the gene expression level can exert a synergistic effect and may potentially supplement cancer therapeutic strategies.