Inhibition of Melanoma Cell Growth by Salvianolic Acid A through CHK2-CDC25A Pathway Modulation

Front Biosci (Landmark Ed). 2024 Jun 12;29(6):213. doi: 10.31083/j.fbl2906213.

Abstract

Background: This study investigated the impact of salvianolic acids, derived from Danshen, on melanoma cell growth. Specifically, we assessed the ability of salvianolic acid A (Sal A) to modulate melanoma cell proliferation.

Methods: We used human melanoma A2058 and A375 cell lines to investigate the effects of Sal A on cell proliferation and death by measuring bromodeoxyuridine incorporation and lactate dehydrogenase release. We assessed cell viability and cycle progression using water soluble tetrazolium salt-1 (WST-1) mitochondrial staining and propidium iodide. Additionally, we used a phospho-kinase array to investigate intracellular kinase phosphorylation, specifically measuring the influence of Sal A on checkpoint kinase-2 (Chk-2) via western blot analysis.

Results: Sal A inhibited the growth of A2058 and A375 cells dose-responsively and induced cell cycle arrest at the G2/M phase. Notably, Sal A selectively induces Chk-2 phosphorylation without affecting Chk-1, thereby degrading Chk-2-regulated genes Cdc25A and Cdc2. However, Sal A does not affect the Chk1-Cdc25C pathway.

Conclusions: Salvianolic acids, especially Sal A, effectively hinder melanoma cell growth by inducing Chk-2 phosphorylation and disrupting G2/M checkpoint regulation.

Keywords: Cdc25A; Chk2; Danshen; melanoma; salvianolic acid A.

MeSH terms

  • Caffeic Acids* / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation* / drug effects
  • Cell Survival / drug effects
  • Checkpoint Kinase 2* / genetics
  • Checkpoint Kinase 2* / metabolism
  • Humans
  • Lactates* / metabolism
  • Lactates* / pharmacology
  • Melanoma* / drug therapy
  • Melanoma* / genetics
  • Melanoma* / metabolism
  • Melanoma* / pathology
  • Phosphorylation / drug effects
  • Signal Transduction / drug effects
  • cdc25 Phosphatases* / genetics
  • cdc25 Phosphatases* / metabolism

Substances

  • Checkpoint Kinase 2
  • cdc25 Phosphatases
  • CHEK2 protein, human
  • salvianolic acid A
  • CDC25A protein, human
  • Lactates
  • Caffeic Acids