Analysis of cell-cycle kinetics and sulfur amino acid metabolism in methionine-dependent tumor cell lines; the effect of homocysteine supplementation

Valérie Pavillard, Abedalnaser A A Drbal, David J. Swaine, Roger M. Phillips, John A. Double, Anna Nicolaou

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Methionine dependence is a feature unique to cancer cells, exhibited as inability to grow in a methionine-depleted environment supplemented with homocysteine, the immediate metabolic precursor of methionine. This study explores the effect of methionine depletion and homocysteine supplementation on the viability, sulfur amino acid metabolism and cell-cycle kinetics of normal and cancer cells, as well as their ability to recover from the treatments. An array of cells including hepatomas (HTC, Phi-1), prostate adenocarcinomas (PC-3) and transformed (3T3) and normal (HS-27) fibroblasts, has been used aiming to evaluate the importance of tissue specificity. All cell lines proliferated well in methionine-complete media (M+H-), whilst only the normal fibroblasts HS-27 grew in methionine-depleted homocysteine-supplemented media (M-H+). None of the tested cell lines were able to grow in media without methionine or homocysteine (M-H-). HTC was the only cell line that did not recover from the M-H+ treatment whilst PC-3 did not recover from the M-H- treatment. Methionine and homocysteine depletion (M-H+ and M-H-) were found to induce arrest at different phases of the cell cycle, depending on the cell line: the methionine-dependent HTC, PC-3 and 3T3 arrested at the S and G2/M phase, whilst Phi-1 and the methionine-independent HS-27 accumulated in the G1 phase. The cell-cycle kinetics showed that the observed blockades were reversible. The information resulting from these studies is important for not only the behavior of cancer cells, but also for appreciating the potential of developing cancer therapies based on methionine-depletion strategies.

Original languageEnglish
Pages (from-to)1587-1599
Number of pages13
JournalBiochemical Pharmacology
Volume67
Issue number8
Early online date25 Feb 2004
DOIs
Publication statusPublished - 15 Apr 2004
Externally publishedYes

Fingerprint

Sulfur Amino Acids
Enzyme kinetics
Homocysteine
Tumor Cell Line
Metabolism
Methionine
Tumors
Cell Cycle
Cells
Cell Line
Fibroblasts
Neoplasms
Organ Specificity
G2 Phase
G1 Phase
Cell Division

Cite this

Pavillard, Valérie ; Drbal, Abedalnaser A A ; Swaine, David J. ; Phillips, Roger M. ; Double, John A. ; Nicolaou, Anna. / Analysis of cell-cycle kinetics and sulfur amino acid metabolism in methionine-dependent tumor cell lines; the effect of homocysteine supplementation. In: Biochemical Pharmacology. 2004 ; Vol. 67, No. 8. pp. 1587-1599.
@article{802d995abed34db9b7536ce4075c0ce1,
title = "Analysis of cell-cycle kinetics and sulfur amino acid metabolism in methionine-dependent tumor cell lines; the effect of homocysteine supplementation",
abstract = "Methionine dependence is a feature unique to cancer cells, exhibited as inability to grow in a methionine-depleted environment supplemented with homocysteine, the immediate metabolic precursor of methionine. This study explores the effect of methionine depletion and homocysteine supplementation on the viability, sulfur amino acid metabolism and cell-cycle kinetics of normal and cancer cells, as well as their ability to recover from the treatments. An array of cells including hepatomas (HTC, Phi-1), prostate adenocarcinomas (PC-3) and transformed (3T3) and normal (HS-27) fibroblasts, has been used aiming to evaluate the importance of tissue specificity. All cell lines proliferated well in methionine-complete media (M+H-), whilst only the normal fibroblasts HS-27 grew in methionine-depleted homocysteine-supplemented media (M-H+). None of the tested cell lines were able to grow in media without methionine or homocysteine (M-H-). HTC was the only cell line that did not recover from the M-H+ treatment whilst PC-3 did not recover from the M-H- treatment. Methionine and homocysteine depletion (M-H+ and M-H-) were found to induce arrest at different phases of the cell cycle, depending on the cell line: the methionine-dependent HTC, PC-3 and 3T3 arrested at the S and G2/M phase, whilst Phi-1 and the methionine-independent HS-27 accumulated in the G1 phase. The cell-cycle kinetics showed that the observed blockades were reversible. The information resulting from these studies is important for not only the behavior of cancer cells, but also for appreciating the potential of developing cancer therapies based on methionine-depletion strategies.",
keywords = "7-fluorobenzofurane-4-sulfonic acid, ammonium salt, AdoMet, Cys, Cys-Gly, Cysteine, Cysteinyl-glycine, DMEM, Dubelcco's modified Eagle medium, Hcy, Homocysteine, MEM, Modified Eagle's medium, Roswell Park Memorial Institute medium, RPMI, S-adenosylmethionine, SBD-f",
author = "Val{\'e}rie Pavillard and Drbal, {Abedalnaser A A} and Swaine, {David J.} and Phillips, {Roger M.} and Double, {John A.} and Anna Nicolaou",
year = "2004",
month = "4",
day = "15",
doi = "10.1016/j.bcp.2004.01.006",
language = "English",
volume = "67",
pages = "1587--1599",
journal = "Biochemical Pharmacology",
issn = "0006-2952",
publisher = "Elsevier Inc.",
number = "8",

}

Analysis of cell-cycle kinetics and sulfur amino acid metabolism in methionine-dependent tumor cell lines; the effect of homocysteine supplementation. / Pavillard, Valérie; Drbal, Abedalnaser A A; Swaine, David J.; Phillips, Roger M.; Double, John A.; Nicolaou, Anna.

In: Biochemical Pharmacology, Vol. 67, No. 8, 15.04.2004, p. 1587-1599.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Analysis of cell-cycle kinetics and sulfur amino acid metabolism in methionine-dependent tumor cell lines; the effect of homocysteine supplementation

AU - Pavillard, Valérie

AU - Drbal, Abedalnaser A A

AU - Swaine, David J.

AU - Phillips, Roger M.

AU - Double, John A.

AU - Nicolaou, Anna

PY - 2004/4/15

Y1 - 2004/4/15

N2 - Methionine dependence is a feature unique to cancer cells, exhibited as inability to grow in a methionine-depleted environment supplemented with homocysteine, the immediate metabolic precursor of methionine. This study explores the effect of methionine depletion and homocysteine supplementation on the viability, sulfur amino acid metabolism and cell-cycle kinetics of normal and cancer cells, as well as their ability to recover from the treatments. An array of cells including hepatomas (HTC, Phi-1), prostate adenocarcinomas (PC-3) and transformed (3T3) and normal (HS-27) fibroblasts, has been used aiming to evaluate the importance of tissue specificity. All cell lines proliferated well in methionine-complete media (M+H-), whilst only the normal fibroblasts HS-27 grew in methionine-depleted homocysteine-supplemented media (M-H+). None of the tested cell lines were able to grow in media without methionine or homocysteine (M-H-). HTC was the only cell line that did not recover from the M-H+ treatment whilst PC-3 did not recover from the M-H- treatment. Methionine and homocysteine depletion (M-H+ and M-H-) were found to induce arrest at different phases of the cell cycle, depending on the cell line: the methionine-dependent HTC, PC-3 and 3T3 arrested at the S and G2/M phase, whilst Phi-1 and the methionine-independent HS-27 accumulated in the G1 phase. The cell-cycle kinetics showed that the observed blockades were reversible. The information resulting from these studies is important for not only the behavior of cancer cells, but also for appreciating the potential of developing cancer therapies based on methionine-depletion strategies.

AB - Methionine dependence is a feature unique to cancer cells, exhibited as inability to grow in a methionine-depleted environment supplemented with homocysteine, the immediate metabolic precursor of methionine. This study explores the effect of methionine depletion and homocysteine supplementation on the viability, sulfur amino acid metabolism and cell-cycle kinetics of normal and cancer cells, as well as their ability to recover from the treatments. An array of cells including hepatomas (HTC, Phi-1), prostate adenocarcinomas (PC-3) and transformed (3T3) and normal (HS-27) fibroblasts, has been used aiming to evaluate the importance of tissue specificity. All cell lines proliferated well in methionine-complete media (M+H-), whilst only the normal fibroblasts HS-27 grew in methionine-depleted homocysteine-supplemented media (M-H+). None of the tested cell lines were able to grow in media without methionine or homocysteine (M-H-). HTC was the only cell line that did not recover from the M-H+ treatment whilst PC-3 did not recover from the M-H- treatment. Methionine and homocysteine depletion (M-H+ and M-H-) were found to induce arrest at different phases of the cell cycle, depending on the cell line: the methionine-dependent HTC, PC-3 and 3T3 arrested at the S and G2/M phase, whilst Phi-1 and the methionine-independent HS-27 accumulated in the G1 phase. The cell-cycle kinetics showed that the observed blockades were reversible. The information resulting from these studies is important for not only the behavior of cancer cells, but also for appreciating the potential of developing cancer therapies based on methionine-depletion strategies.

KW - 7-fluorobenzofurane-4-sulfonic acid, ammonium salt

KW - AdoMet

KW - Cys

KW - Cys-Gly

KW - Cysteine

KW - Cysteinyl-glycine

KW - DMEM

KW - Dubelcco's modified Eagle medium

KW - Hcy

KW - Homocysteine

KW - MEM

KW - Modified Eagle's medium

KW - Roswell Park Memorial Institute medium

KW - RPMI

KW - S-adenosylmethionine

KW - SBD-f

UR - http://www.scopus.com/inward/record.url?scp=1642318462&partnerID=8YFLogxK

UR - https://www.sciencedirect.com/journal/biochemical-pharmacology

U2 - 10.1016/j.bcp.2004.01.006

DO - 10.1016/j.bcp.2004.01.006

M3 - Article

VL - 67

SP - 1587

EP - 1599

JO - Biochemical Pharmacology

JF - Biochemical Pharmacology

SN - 0006-2952

IS - 8

ER -