Gallic acid induces apoptosis in A375.S2 human melanoma cells through caspase-dependent and -independent pathways

Int J Oncol. 2010 Aug;37(2):377-85. doi: 10.3892/ijo_00000686.


The natural antioxidant gallic acid (GA) has demonstrated a significant inhibition of cell proliferation and induction of apoptosis in a series of cancer cell lines. However, there is no available information to show whether GA induces apoptosis in human skin cancer cells. In the present study, we report GA-induced apoptosis in A375.S2 human melanoma cells. GA affected morphological changes, decreased the percentage of viable cells and induced apoptosis in A375.S2 cells in a dose- and time-dependent manner. Observation of the molecular mechanism of apoptosis in A375.S2 cells showed that GA up-regulated the proapoptotic proteins such as Bax, and induced caspase cascade activity, but down-regulated antiapoptotic proteins such as Bcl-2. GA induced reactive oxygen species (ROS) and intracellular Ca2+ productions and decreased the level of mitochondrial membrane potential (DeltaPsim) in A375.S2 cells in a time-dependent manner. GA triggered cytosolic release of apoptotic molecules, cytochrome c, promoted activation of caspase-9 and caspase-3, and ultimately apoptotic cell death. In addition, GA also promoted cytosolic release of apoptosis-inducing factor (AIF) and endonuclease G (Endo G). Therefore, GA may also induce apoptosis through a caspase-independent pathway. Our results suggest that GA might be a potential anticancer compound; however, in depth in vivo studies are needed to elucidate the exact mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / metabolism
  • Calcium / metabolism
  • Caspases / metabolism
  • Caspases / physiology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cytochromes c / metabolism
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Gallic Acid / pharmacology*
  • Humans
  • Melanoma / metabolism
  • Melanoma / pathology*
  • Membrane Potential, Mitochondrial / drug effects
  • Models, Biological
  • Protein Transport / drug effects
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / physiology


  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • Reactive Oxygen Species
  • Gallic Acid
  • Cytochromes c
  • Caspases
  • Calcium