Humic acid induces apoptosis in human premyelocytic leukemia HL-60 cells

Life Sci. 2004 Aug 27;75(15):1817-31. doi: 10.1016/j.lfs.2004.02.033.


It has been shown that humic acid (HA), a phenolic polymer, exhibits pro-oxidant and cytotoxic effects. In this study, HA induction of apoptosis was studied using cultured human premyelocytic leukemia HL-60 cells. Treatment at a range of HA concentrations (50-400 microg/ml) resulted in dose-and time-dependent sequences of events marked by apoptosis, as demonstrated through by apoptotic features such as loss of cell viability, chromatin condensation, and internucleosomal DNA fragmentation. This HA-induced apoptosis in the HL-60 cells was mainly associated with the release of cytochrome c from the mitochondria. Furthermore, apoptosis in the HL-60 cells was accompanied by the activation of caspase-3 and the specific proteolytic cleavage of poly (ADP-ribose) polymerase (PARP), a major component in the apoptotic cell death mechanism. Although the HA-induced apoptosis was associated with Bax protein levels, negligible Bcl-2 reduction was observed. Analysis of the data reported herein reveals that HA exerts antiproliferative action and growth inhibition on HL-60 cells through induction of apoptosis, which may have anticancer properties potentially useful for the development of new drug products.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Blotting, Western
  • Caspase 3
  • Caspases / metabolism
  • Cell Division / drug effects
  • Cell Survival / drug effects
  • Cytochromes c / metabolism
  • DNA Fragmentation / drug effects
  • Electrophoresis, Agar Gel
  • HL-60 Cells
  • Humans
  • Humic Substances*
  • In Situ Nick-End Labeling
  • Nitric Oxide / metabolism
  • Paclitaxel / pharmacology
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases
  • Proteins / metabolism
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • bcl-2-Associated X Protein


  • Antineoplastic Agents, Phytogenic
  • BAX protein, human
  • Humic Substances
  • Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Nitric Oxide
  • Cytochromes c
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases
  • CASP3 protein, human
  • Caspase 3
  • Caspases
  • Paclitaxel