PMID- 15370221
OWN - NLM
STAT- MEDLINE
DCOM- 20041221
LR  - 20190116
IS  - 1042-8194 (Print)
IS  - 1026-8022 (Linking)
VI  - 45
IP  - 8
DP  - 2004 Aug
TI  - Citrate shows specific, dose-dependent lympholytic activity in neoplastic cell 
      lines.
PG  - 1657-65
AB  - We have demonstrated cell membrane destruction activity by carboxylic acid 
      derivatives (CADs) mainly tri-sodium citrate, in neoplastic cell lines and, to a 
      far lesser extent, in normal human peripheral blood mononuclear cells (hPBMC). 
      Flow cytometric (FACS) analysis was applied to Annexin-V and Propidium Iodide 
      (PI) stained cells to evaluate the degree of the apoptosis induced by citrate in 
      the following cell lines: CCRF-CEM (shortened to CEM), H9, and Jurkat (T-Cells), 
      Raji and WIL2-NS (B-Cells), HL-60 (myeloblasts), K562 (myelocytes) and U937 
      (monocytes). We also tested normal hPBMC. Before staining with Annexin/PI, manual 
      cell counts were performed on 24- and 48-h-old cell cultures. Cell supernatants 
      were assayed for lactate dehydrogenase (LDH). LDH values in samples correlated 
      with enhanced apoptosis by FACS analysis. For comparison, ascorbate and 2 other 
      CADs including, acetate and lactate were also evaluated for the induction of 
      apoptosis. In addition, the ability of tri-sodium citrate to induce apoptosis in 
      the presence and the absence of several antineoplastic drugs, such as 
      dexamethasone, arsenic trioxide, hydrocortisone, 6-mercaptopurine, and 
      methotrexate were tested on Jurkat cells. FACS, LDH, and cell count values all 
      demonstrated an enhanced degree of apoptotic cell death in Jurkat cells by 
      citrate. In most of our investigated cells, except for the H9 cell line, citrate 
      has induced a greater degree of apoptosis than acetate which induced a greater 
      degree than lactate (see Fig. 1.0). The nature of the cell death by ascorbate 
      appeared to be due to necrosis rather than apoptosis. Pilot studies on normal 
      hPBMC showed that citrate alone or in combination with antineoplastic drugs 
      caused minimal cell death. Thus citrate might be of benefit in some chemotherapy 
      treatments in order to reduce drug toxicity or possibly enhance drug activities 
      in certain neoplasias.
FAU - Yousefi, S
AU  - Yousefi S
AD  - University of California, Irvine Medical Center, Orange, CA 92868, USA. 
      jshookoo@uci.edu
FAU - Owens, J W
AU  - Owens JW
FAU - Cesario, T C
AU  - Cesario TC
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Leuk Lymphoma
JT  - Leukemia & lymphoma
JID - 9007422
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Citrates)
RN  - 0 (Drug Combinations)
RN  - 1Q73Q2JULR (Sodium Citrate)
RN  - 33X04XA5AT (Lactic Acid)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - PQ6CK8PD0R (Ascorbic Acid)
RN  - Q40Q9N063P (Acetic Acid)
SB  - IM
MH  - Acetic Acid/pharmacology
MH  - Antineoplastic Agents/*administration & dosage
MH  - Apoptosis/*drug effects
MH  - Ascorbic Acid/pharmacology
MH  - Citrates/*administration & dosage
MH  - Dose-Response Relationship, Drug
MH  - Drug Combinations
MH  - Flow Cytometry
MH  - Humans
MH  - L-Lactate Dehydrogenase/metabolism
MH  - Lactic Acid/pharmacology
MH  - Leukocytes, Mononuclear/metabolism
MH  - Lymphocytes/*drug effects/pathology
MH  - Necrosis
MH  - Pilot Projects
MH  - Sodium Citrate
MH  - Tumor Cells, Cultured/drug effects/pathology
EDAT- 2004/09/17 05:00
MHDA- 2004/12/22 09:00
CRDT- 2004/09/17 05:00
PHST- 2004/09/17 05:00 [pubmed]
PHST- 2004/12/22 09:00 [medline]
PHST- 2004/09/17 05:00 [entrez]
AID - QJWJRPJG403DMQ2W [pii]
AID - 10.1080/10428190310001603920 [doi]
PST - ppublish
SO  - Leuk Lymphoma. 2004 Aug;45(8):1657-65. doi: 10.1080/10428190310001603920.