NATPRO Journal

Therapeutic Efficacy of Luteolin Against Phorbol 12-Myristate 13-Acetate-Induced Cytotoxicity, Oxidative Stress, and Inflammation in HaCaT Cells 

Received: October 13, 2025; Revised: December 4, 2025; Accepted: January 14, 2026; Published: January 24, 2026

NATPRO J (2026) 3: 1-8 Article

Authors: Himanshi Gahlot1 and Sun Chul Kang1,2*

1Department of Biotechnology, Daegu University, Gyeongsan, 38453, Republic of Korea. 2Dr. Kang Bio Co. Ltd., Gyeongsan, 38428, Republic of Korea

https://doi.org/10.23177/NJ025.1003

Abstract: Phorbol 12-myristate 13-acetate (PMA), a potent protein kinase C activator, is a well-established agent that triggers cytotoxicity, oxidative stress, and inflammation. This study investigated the cytoprotective potential of the natural flavonoid luteolin against PMA-induced toxicity in human HaCaT keratinocytes. We demonstrate for the first time that pre-treatment with luteolin significantly alleviates PMA-induced cytotoxicity in HaCaT cells, evidenced by increased cell viability, reduced LDH release, and enhanced clonogenic survival. Mechanistically, luteolin attenuated oxidative stress by scavenging ROS/NO generation, reducing lipid peroxidation (MDA), and restoring antioxidants (GSH, TRX). Luteolin further prevented the PMA-induced elevation of inflammatory mediators (NF-κB, COX-2, IL-6, and IL-1β) and associated DNA damage indicators (γ-H2AX, ERCC1). These findings reveal that luteolin possesses significant cytoprotective, antioxidant, and anti-inflammatory properties against PMA-induced damage, underscoring its potential as a therapeutic agent for inflammatory skin disorders. Future validation in more complex physiological models is warranted to bridge these promising in vitro results to potential clinical applications addressing PMA-related pathologies. 

Keywords: luteolin, PMA, HaCaT, inflammation, ROS, NF-κB