# Apoptosis, Cell Growth, and Glycogen Synthase Kinase 3β Phosphorylation in Caffeic Acid-Treated Human Malignant Melanoma Cells

## TL;DR

Caffeic acid reduces melanoma cell growth by activating the p53 tumor suppressor pathway, not through GSK3β signaling.

## Contribution

This study reveals a novel mechanism of caffeic acid's anti-melanoma activity via p53 pathway activation.

## Key findings

- Caffeic acid decreased melanoma cell viability and induced apoptosis.
- Caffeic acid upregulated p53 and p21 while downregulating cyclin D1 and Bcl-2.
- Melanoma tissues showed significantly higher p-GSK3β levels compared to normal skin.

## Abstract

Objectives: Caffeic acid (CA), a naturally occurring phenolic compound exhibiting antioxidant and anti-inflammatory effects, has demonstrated anticancer activity against several tumor types. Nevertheless, its involvement in melanoma and its effects on the GSK3β signaling pathway have not been fully elucidated. This study aimed to assess the expression of p-GSK3β in melanoma tissues and to evaluate the anti-melanoma efficacy of CA. Methods: Western blot analysis was performed to determine the expression levels of p-GSK3β in melanoma and normal skin samples. G361 melanoma cells were exposed to CA, after which cell viability, apoptotic induction, cell cycle distribution, and related signaling molecules were examined. Results: Significantly increased p-GSK3β levels were identified in melanoma tissues. CA exposure decreased cell viability, triggered apoptosis, and elevated p-GSK3β levels in G361 melanoma cells. Moreover, CA induced the upregulation of p53 and p21 while concomitantly downregulating cyclin D1 and Bcl-2. Conclusions: These results suggest that CA inhibits melanoma cell growth through activation of a pathway involving the tumor suppressor p53, rather than through modulation of GSK3β signaling.