Vitamin C Research Today is a free monthly online journal that collates and summarizes the latest research about Vitamin C, including details on benefits, dosage, supplements, information.

Activation of Raf1 and the ERK pathway in response to l-ascorbic acid in acute myeloid leukemia cells.

Park S, Park CH, Hahm ER, Kim K, Kimler BF, Lee SJ, Park HK, Lee SH, Kim WS, Jung CW, Park K, Riordan HD, Lee JH

Samsung Medical Center and Sungkyunkwan University School of Medicine, Seoul 135-710, Korea. sypark21@yumc.yonsei.ac.kr

L-ascorbic acid (LAA) shows cytotoxicity and induces apoptosis of malignant cells in vitro, but the mechanisms by which such effects occur have not been elucidated. In the present study, we provide evidence that the ERK MAP kinase pathway is activated in response to LAA (< 1 mM) in acute myeloid leukemia cell lines. LAA treatment of cells induces a dose-dependent phosphorylation of extracellular signal-regulated kinases (ERK) and results in activation of its catalytic domain. Our data also demonstrate that the small G protein Raf1 and MAPK-activated protein kinase 2 are activated by LAA as an upstream and a downstream regulator of ERK, respectively. Although the ERK pathway has been known to activate cell proliferation, pharmacologic inhibition of ERK reduces LAA-dependent apoptosis and growth inhibitory response of acute myeloid leukemia cell lines, suggesting that this signaling cascade positively regulates induction of apoptotic response by LAA.

Published 28 September 2004 in Cell Signal, 17(1): 111-9.
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