title: Enhancement of plasmacytoma cell growth by ascorbic acid is mediated via glucose 6-phosphate dehydrogenase.
abstract: OBJECTIVE
  We investigated the mechanism by which some types of cancer cells grow faster in the presence of ascorbic acid supplementation.
  
  
  METHODS
  Adj.PC-5, a mouse plasmacytoma cell, is known to show ascorbic acid-dependent growth and was chosen as a test system. The growth of cancer cells was measured by the colony number on soft agar or the cellular proliferation in suspension culture. The ascorbate level was measured by a high performance liquid chromatography system with an electrochemical detector. Glucose 6-phosphate dehydrogenase was analyzed both on the specific enzyme activity level and on the transcription level by performing Northern blot analysis.
  
  
  RESULTS
  Ascorbyl 2-phosphate among the ascorbate derivatives was the most efficient in stimulating cell growth. The intracellular and extracellular ascorbate concentrations following treatment with either ascorbate or ascorbyl 2-phosphate suggest that the superiority of ascorbyl 2-phosphate for stimulating cell growth may be due to its slow conversion to ascorbate in the culture medium. The steady transformation to ascorbate ensures sustained levels of ascorbate in the culture medium and thereby maximizes the growth stimulatory effect of ascorbate. Ascorbyl 2-phosphate markedly enhanced, in a concentration-and time-dependent manner, mRNA synthesis as well as the enzymatic activity of glucose 6-phosphate dehydrogenase, which is known to be a rate-limiting enzyme in cell growth. On the other hand, simultaneous addition of dehydroisoandrosterone, a well- known inhibitor of glucose 6-phosphate dehydrogenase, to the culture medium abrogated the growth stimulation by ascorbyl 2-phosphate, and it also reduced the glucose 6-phosphate dehydrogenase activity proportionately.
  
  
  CONCLUSIONS
  The results from this study suggest that enhanced glucose 6-phosphate dehydrogenase activity may at least in part explain the stimulation of cell growth by ascorbate or ascorbyl 2-phosphate.
authors.affiliation: Korea Institute of Toxicology, Daejeon, Korea. wskoh@kitox.re.kr
authors.forename: Woo Suk
authors.initials: WS
authors.lastname: Koh
authors.forename: Woo Hyuck
authors.initials: WH
authors.lastname: Choi
authors.forename: Sook Ja
authors.initials: SJ
authors.lastname: Lee
authors.forename: Chaehwa
authors.initials: C
authors.lastname: Park
authors.forename: Chan H
authors.initials: CH
authors.lastname: Park