An evaluation of the role of glutathione and its associated enzymes in the expression of differential sensitivities to antitumour agents shown by a range of human tumour cell lines

Hosking, Louise K.; Whelan, Richard D. H.; Shellard, Sharon A.; Bedford, Philip; Hill, Bridget T.

doi:10.1016/0006-2952(90)90364-q

Cited by 89 publications

(32 citation statements)

References 42 publications

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“…The concentration value of 17.3+4.7 nmol/10 6 cells, corresponding to 75.2+20.0 nmol/mg protein, measured for glutathione in SK-OV-3, was in good agreement with that previously reported by Hosking et al, 1990, for the same cell line (80.7+18.0 nmol/mg protein).…”

Section: H Nmr Detects Polyol Accumulation In Ovarian Caba I Cells a supporting

confidence: 91%

“…In particular, the role of the glutathione system in the development and maintenance of multi-drug resistance has been demonstrated in some tumour cells (Hosking et al, 1990;Ferretti et al, 1993). Regarding myo-inositol, although the complexity of the pathways responsible for the synthesis and turnover of this metabolite so far prevented a clear elucidation of the role of this compound in cerebral tumours and in some cognitive diseases, the view is growing that myo-inositol does not act as a simple osmolyte (Ross, 2000).…”

Section: Discussionmentioning

confidence: 99%

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Detection of polyol accumulation in a new ovarian carcinoma cell line, CABA I: a1H NMR study

et al. 2002

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Ovarian carcinomas represent a major form of gynaecological malignancies, whose treatment consists mainly of surgery and chemotherapy. Besides the difficulty of prognosis, therapy of ovarian carcinomas has reached scarce improvement, as a consequence of lack of efficacy and development of drug-resistance. The need of different biochemical and functional parameters has grown, in order to obtain a larger view on processes of biological and clinical significance. In this paper we report novel metabolic features detected in a series of different human ovary carcinoma lines, by 1 H NMR spectroscopy of intact cells and their extracts. Most importantly, a new ovarian adenocarcinoma line CABA I, showed strong signals in the spectral region between 3.5 and 4.0 p.p.m., assigned for the first time to the polyol sorbitol (39+11 nmol/10 6 cells). 13 C NMR analyses of these cells incubated with [1-13 C]-D-glucose demonstrated labelled-sorbitol formation. The other ovarian carcinoma cell lines (OVCAR-3, IGROV 1, SK-OV-3 and OVCA432), showed, in the same spectral region, intense resonances from other metabolites: glutathione (up to 30 nmol/10 6 cells) and myo-inositol (up to 50 nmol/10 6 cells). Biochemical and biological functions are suggested for these compounds in human ovarian carcinoma cells, especially in relation to their possible role in cell detoxification mechanisms during tumour progression.

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Section: H Nmr Detects Polyol Accumulation In Ovarian Caba I Cells a supporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Detection of polyol accumulation in a new ovarian carcinoma cell line, CABA I: a1H NMR study

et al. 2002

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“…High GSH levels may mediate resistance towards both radiation therapy and treatment with some anti-cancer drug regimens (33)(34)(35). Buthionine sulfoximine, a specific inhibitor of GSH synthesis, circumvents cisplatin resistance in human head and neck squamous cell carcinomas grown in nude mice (36).…”

Section: Discussionmentioning

confidence: 99%

Glutathione S-transferases and glutathione in human head and neck cancer

Mulder¹,

Manni

Roelofs³

et al. 1995

Carcinogenesis

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Glutathione S-transferase (GST) enzyme activity, GST isoenzyme composition and glutathione (GSH) concentra tion were assessed in normal and squamous cell carcinoma specimens of 14 patients with oral or oropharyngeal cancer and 11 patients with laryngeal cancer. Comparing malig nant with normal oral/oropharyngeal tissues, no significant differences in GSH content, GST enzyme activity or iso enzyme composition were found. However, some tumours had up to 3-fold increased GST enzyme activities and 11 malignant samples over-expressed GST-tc. GST-tc was present in all normal and malignant oral/oropharyngeal specimens investigated, whereas class a and class \i were detected in only a few samples. GST-fj. was present in 28% of the patients with oral/oropharyngeal tumours as compared with -60% in the normal population. GST-a, -|i and -71 were detected in 91, 64 and 100% of the normal laryngeal tissues respectively. In laryngeal tumours signi ficantly higher levels of GST-tc and GSH but signi ficantly lower amounts of GST-a were detected. Levels of class p GST were generally lower in cancerous tissues, but differences were not significant. In comparison with normal oral/oropharyngeal tissues, normal laryngeal tissues con tained almost twice the amount of GST enzyme activity due to higher class a enzyme levels. It is concluded that (ÏST-7C is elevated in 11 out of 14 tumours of the oral cavity and values are significantly increased in tumours of the larynx, which may contribute to the inherent anti-cancer drug resistance of these malignancies. In laryngeal tumours the increased GSH levels may confer additional resistance to radiation therapy.

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“…models, increased cellular GSH or activity of GSH-dependent enzymes can produce resistance to a wide range of cytotoxic drugs, including alkylating agents, cisplatin and anthracyclines, and under some circumstances to radiation therapy (Barrancoa et al, 1990;Hosking et al, 1990). Furthermore, experimental animal tumours show considerable heterogeneity in GSH content (Shrieve et al, 1988;, and viable cell sorting following exposure to drugs or radiation in vivo shows greater clonogemic survival in cells with high GSH content .…”

Section: Discussomentioning

confidence: 99%

Differential effects of depleting agents on cytoplasmic and nuclear non-protein sulphydryls: a fluorescence image cytometry study

Thomas

Nicklee²,

Hedley³

1995

Br J Cancer

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An evaluation of the role of glutathione and its associated enzymes in the expression of differential sensitivities to antitumour agents shown by a range of human tumour cell lines

Cited by 89 publications

References 42 publications

Detection of polyol accumulation in a new ovarian carcinoma cell line, CABA I: a1H NMR study

Detection of polyol accumulation in a new ovarian carcinoma cell line, CABA I: a1H NMR study

Glutathione S-transferases and glutathione in human head and neck cancer

Differential effects of depleting agents on cytoplasmic and nuclear non-protein sulphydryls: a fluorescence image cytometry study

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