Methionine dependence of tumours

A biochemical strategy for optimizing paclitaxel chemosensitivity in vitro

Valerie Pavillard, Anna Nicolaou, John A. Double, Roger M. Phillips

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Methionine dependence is a unique feature of cancer cells characterized by growth and cell cycle arrest (typically in S and G2/M) under conditions of methionine depletion. Following replenishment of media with methionine, the cell cycle blockade is reversible and during this recovery period, cells may become more susceptible to the action of cell cycle specific drugs. The response of a panel of methionine dependent (HTC, Phi-1, PC3 and 3T3) cells to vinblastine and paclitaxel was compared to methionine independent Hs-27 cells under conditions of methionine depletion (M-H+; methionine depleted media supplemented with homocysteine) and starvation (M-H-; media without methionine or homocysteine). All cell lines were significantly more resistant to both agents under M-H+ and M -H- conditions compared to controls under normal culture conditions [M+H-]; however, the magnitude of resistance was reduced in the methionine independent Hs-27 cells. During recovery from methionine depletion and starvation, the response of the methionine dependent cells to vinblastine and paclitaxel was significantly enhanced compared to controls. Although the activity of vinblastine on the Hs-27 cell line was comparable to controls, these methionine independent cells became significantly more resistant to paclitaxel during recovery studies (IC50 = 2.13 ± 0.5 μM) compared to control cultures (IC50 = 0.13 ± 0.15 μM). Whilst the mechanism responsible for this remains uncertain, the increased activity of paclitaxel against methionine dependent cells in conjunction with the decreased activity against Hs-27 cells suggests that methionine depletion strategies may enhance the therapeutic index of paclitaxel.

Original languageEnglish
Pages (from-to)772-778
Number of pages7
JournalBiochemical Pharmacology
Volume71
Issue number6
Early online date18 Jan 2006
DOIs
Publication statusPublished - 14 Mar 2006
Externally publishedYes

Fingerprint

Paclitaxel
Methionine
Tumors
Neoplasms
Cells
Vinblastine
Homocysteine
Starvation
In Vitro Techniques
Recovery
Inhibitory Concentration 50
Cell Cycle
Cell Line
3T3 Cells
Cell Cycle Checkpoints

Cite this

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abstract = "Methionine dependence is a unique feature of cancer cells characterized by growth and cell cycle arrest (typically in S and G2/M) under conditions of methionine depletion. Following replenishment of media with methionine, the cell cycle blockade is reversible and during this recovery period, cells may become more susceptible to the action of cell cycle specific drugs. The response of a panel of methionine dependent (HTC, Phi-1, PC3 and 3T3) cells to vinblastine and paclitaxel was compared to methionine independent Hs-27 cells under conditions of methionine depletion (M-H+; methionine depleted media supplemented with homocysteine) and starvation (M-H-; media without methionine or homocysteine). All cell lines were significantly more resistant to both agents under M-H+ and M -H- conditions compared to controls under normal culture conditions [M+H-]; however, the magnitude of resistance was reduced in the methionine independent Hs-27 cells. During recovery from methionine depletion and starvation, the response of the methionine dependent cells to vinblastine and paclitaxel was significantly enhanced compared to controls. Although the activity of vinblastine on the Hs-27 cell line was comparable to controls, these methionine independent cells became significantly more resistant to paclitaxel during recovery studies (IC50 = 2.13 ± 0.5 μM) compared to control cultures (IC50 = 0.13 ± 0.15 μM). Whilst the mechanism responsible for this remains uncertain, the increased activity of paclitaxel against methionine dependent cells in conjunction with the decreased activity against Hs-27 cells suggests that methionine depletion strategies may enhance the therapeutic index of paclitaxel.",
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Methionine dependence of tumours : A biochemical strategy for optimizing paclitaxel chemosensitivity in vitro. / Pavillard, Valerie; Nicolaou, Anna; Double, John A.; Phillips, Roger M.

In: Biochemical Pharmacology, Vol. 71, No. 6, 14.03.2006, p. 772-778.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Methionine dependence of tumours

T2 - A biochemical strategy for optimizing paclitaxel chemosensitivity in vitro

AU - Pavillard, Valerie

AU - Nicolaou, Anna

AU - Double, John A.

AU - Phillips, Roger M.

PY - 2006/3/14

Y1 - 2006/3/14

N2 - Methionine dependence is a unique feature of cancer cells characterized by growth and cell cycle arrest (typically in S and G2/M) under conditions of methionine depletion. Following replenishment of media with methionine, the cell cycle blockade is reversible and during this recovery period, cells may become more susceptible to the action of cell cycle specific drugs. The response of a panel of methionine dependent (HTC, Phi-1, PC3 and 3T3) cells to vinblastine and paclitaxel was compared to methionine independent Hs-27 cells under conditions of methionine depletion (M-H+; methionine depleted media supplemented with homocysteine) and starvation (M-H-; media without methionine or homocysteine). All cell lines were significantly more resistant to both agents under M-H+ and M -H- conditions compared to controls under normal culture conditions [M+H-]; however, the magnitude of resistance was reduced in the methionine independent Hs-27 cells. During recovery from methionine depletion and starvation, the response of the methionine dependent cells to vinblastine and paclitaxel was significantly enhanced compared to controls. Although the activity of vinblastine on the Hs-27 cell line was comparable to controls, these methionine independent cells became significantly more resistant to paclitaxel during recovery studies (IC50 = 2.13 ± 0.5 μM) compared to control cultures (IC50 = 0.13 ± 0.15 μM). Whilst the mechanism responsible for this remains uncertain, the increased activity of paclitaxel against methionine dependent cells in conjunction with the decreased activity against Hs-27 cells suggests that methionine depletion strategies may enhance the therapeutic index of paclitaxel.

AB - Methionine dependence is a unique feature of cancer cells characterized by growth and cell cycle arrest (typically in S and G2/M) under conditions of methionine depletion. Following replenishment of media with methionine, the cell cycle blockade is reversible and during this recovery period, cells may become more susceptible to the action of cell cycle specific drugs. The response of a panel of methionine dependent (HTC, Phi-1, PC3 and 3T3) cells to vinblastine and paclitaxel was compared to methionine independent Hs-27 cells under conditions of methionine depletion (M-H+; methionine depleted media supplemented with homocysteine) and starvation (M-H-; media without methionine or homocysteine). All cell lines were significantly more resistant to both agents under M-H+ and M -H- conditions compared to controls under normal culture conditions [M+H-]; however, the magnitude of resistance was reduced in the methionine independent Hs-27 cells. During recovery from methionine depletion and starvation, the response of the methionine dependent cells to vinblastine and paclitaxel was significantly enhanced compared to controls. Although the activity of vinblastine on the Hs-27 cell line was comparable to controls, these methionine independent cells became significantly more resistant to paclitaxel during recovery studies (IC50 = 2.13 ± 0.5 μM) compared to control cultures (IC50 = 0.13 ± 0.15 μM). Whilst the mechanism responsible for this remains uncertain, the increased activity of paclitaxel against methionine dependent cells in conjunction with the decreased activity against Hs-27 cells suggests that methionine depletion strategies may enhance the therapeutic index of paclitaxel.

KW - Chemosensitivity

KW - Homocysteine

KW - Methionine-dependence

KW - Paclitaxel

KW - Vinblastine

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U2 - 10.1016/j.bcp.2005.12.014

DO - 10.1016/j.bcp.2005.12.014

M3 - Article

VL - 71

SP - 772

EP - 778

JO - Biochemical Pharmacology

JF - Biochemical Pharmacology

SN - 0006-2952

IS - 6

ER -