L-Ascorbic acid induces apoptosis in acute myeloid leukemia cells via hydrogen peroxide-mediated mechanisms

Seyeon Park, Seong Su Han, Chan H. Park, Eun Ryeong Hahm, Sook J. Lee, Hye K. Park, Se Hoon Lee, Won S. Kim, Chul Won Jung, Keunchil Park, Hugh D. Riordan, Bruce F. Kimler, Kihyun Kim, Je Ho Lee

Research output: Contribution to journalArticlepeer-review

79 Scopus citations


L-Ascorbic acid (LAA) is being investigated clinically for the treatment of patients with acute myeloid leukemia (AML) based on the observed effects of LAA on AML progenitor cells in vitro. However, the mechanism for LAA-induced cytoreduction remains to be elucidated. LAA at concentrations of 0.25-1.0 mM induced a dose- and time-dependent inhibition of proliferation in three AML cell lines and also in leukemic cells from peripheral blood specimens obtained from three patients with AML. In contrast, ovarian cancer cell lines were only minimally affected. Flow cytometric analysis showed that LAA at concentrations of 0.25-1.0 mM could significantly induce apoptosis in the AML cell lines. LAA induced oxidation of glutathione to oxidized form (GSSG) and subsequent H 2O 2 accumulation in a concentration-dependent manner, in parallel to induction of apoptosis. The direct role of H 2O 2 in the induction of apoptosis in AML cells was clearly demonstrated by the finding that catalase could completely abrogate LAA-induced apoptosis. Induction of apoptosis in LAA-treated AML cells involved a dose-dependent increase of Bax protein, release of cytochrome C from mitochondria to cytosol, activation of caspase 9 and caspase 3, and cleavage of poly[ADP-ribose] polymerase. In conclusion, LAA can induce apoptosis in AML cells, and this is clearly due to H 2O 2 which accumulates intracellularly as a result of oxidation of reduced glutathione by LAA.

Original languageEnglish (US)
Pages (from-to)2180-2195
Number of pages16
JournalInternational Journal of Biochemistry and Cell Biology
Issue number11
StatePublished - Nov 2004

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cell Biology


Dive into the research topics of 'L-Ascorbic acid induces apoptosis in acute myeloid leukemia cells via hydrogen peroxide-mediated mechanisms'. Together they form a unique fingerprint.

Cite this