Chemoprevention of lotus leaf ethanolic extract through epigenetic activation of the NRF2-mediated pathway in murine skin JB6 P+ cell neoplastic transformation

Yen-Chen Tung; Ping-Hua Sung; Pei-Chun Chen; Hsiao Chi Wang; Jong Hun Lee; Zheng-Yuan Su

doi:10.1016/j.jtcme.2023.02.002

Chemoprevention of lotus leaf ethanolic extract through epigenetic activation of the NRF2-mediated pathway in murine skin JB6 P+ cell neoplastic transformation

J Tradit Complement Med. 2023 Feb 25;13(4):337-344. doi: 10.1016/j.jtcme.2023.02.002. eCollection 2023 Jul.

Authors

Yen-Chen Tung¹, Ping-Hua Sung², Pei-Chun Chen², Hsiao Chi Wang³, Jong Hun Lee⁴, Zheng-Yuan Su²

Affiliations

¹ Department of Food Science, National Ilan University, Yilan County, 260007, Taiwan.
² Department of Bioscience Technology, Chung Yuan Christian University, Taoyuan City, 320314, Taiwan.
³ Department of Oral Hygiene and Healthcare, Cardinal Tien Junior College of Healthcare and Management, New Taipei City, 23143, Taiwan.
⁴ Department of Food Science and Biotechnology, Gachon University, Seongnam, 13120, South Korea.

Abstract

Background and aim: Skin is one barrier protecting from environmental risk factors that can make skin cells cancerous through DNA damage and oxidative stress. The nuclear factor erythroid 2-related factor 2 (NRF2) pathway is an anti-stress defense system that can be regulated by DNA methylation and histone modification. Dietary phytochemicals have chemopreventive properties that can inhibit or delay carcinogenesis. The lotus leaf is a traditional medicinal plant containing many polyphenols whose extracts show many biological activities, including antioxidant, anti-obesity, and anti-cancer. This study aim to investigate the effect of lotus leaves on neoplastic transformation in murine skin JB6 P+ cells.

Experimental procedure: Lotus leaves were extracted with water (LL-WE) and ethanol (LL-EE), and the LL-WE residues were further extracted with ethanol (LL-WREE). JB6 P+ cells were treated with different extracts. The chemoprotective effect would be evaluated by heme oxygenase 1 (HO-1), NAD(P)H quinone oxidoreductase (NQO1), and UDP glucuronosyltransferase family 1 member A1 (UGT1A1) expression.

Results and conclusion: LL-EE contained higher total phenolics and quercetin among extracts. In mouse skin JB6 P+ cells with 12-O-tetradecanoylphorbol-13-acetate treatment, LL-EE showed the greatest potential to suppress skin carcinogenesis. LL-EE activated the NRF2 pathway by upregulating antioxidant and detoxification enzymes upregulates antioxidant and detoxification enzymes, including HO-1, NQO1, and UGT1A1, and downregulates DNA methylation, which might be caused by lower DNA methyltransferase and histone deacetylase levels. Therefore, our results show that LL-EE reduces the neoplastic transformation of skin JB6 P+ cells, potentially by activating the NRF2 pathway and regulating epigenetic DNA methylation and histone acetylation.

Keywords: Antioxidant; Cancer transformation; DNA methylation; Herbal medicine; Skin cell.