Cellular Glutathione Content, in Vitro Chemoresponse, and the Effect of BSO Modulation in Samples Derived from Patients with Advanced Ovarian Cancer

doi:10.1006/gyno.2002.6617

Gynecologic Oncology

Volume 85, Issue 2, May 2002, Pages 298-304

https://doi.org/10.1006/gyno.2002.6617 Get rights and content

Abstract

Objectives. The objective was to assess the relationship between glutathione content and drug sensitivity with glutathione modulation in ovarian cancer in a pilot study using 31 samples of freshly obtained ovarian tumor material from 26 patients with advanced disease.

Methods. Processed tumor samples were screened to determine the glutathione content using an enzyme recycling assay modified for use in a 96-well plate format. Chemosensitivity testing (MTT assay) was used to assess sensitivity to cisplatin and doxorubicin and modulation using buthionine sulfoximine. Multidrug-resistance-associated protein MRP1 (putative drug–glutathione conjugate transporter) expression was also assessed.

Results. There was a significant increase in the tumor cell GSH levels in samples from patients who had received previous chemotherapy (9) versus those from chemotherapy-naı̈ve patients (20), P = 0.005. In vitro chemosensitivity testing with doxorubicin and cisplatin (using LC₅₀ values, i.e., drug dose causing 50% reduction in cell survival relative to untreated control) failed to show a relationship with glutathione levels. Coincubation of cisplatin and doxorubicin with buthionine sulfoximine resulted in a significant increase in sensitivity to both of these drugs overall (cisplatin, P = 0.05; doxorubicin, P = 0.025), with 20 samples showing sensitization to a drug to which they were previously resistant. MRP1 expression failed to show a correlation with drug sensitivity and glutathione levels.

Conclusions. Our study supports the use of glutathione modulation using agents such as buthionine sulfoximine in patients with heavily pretreated, drug-resistant ovarian cancer.

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Regular ArticleCellular Glutathione Content, in Vitro Chemoresponse, and the Effect of BSO Modulation in Samples Derived from Patients with Advanced Ovarian Cancer

Abstract

Int J Radiation Oncol Biol Phys

J Biol Chem

Anal Biochem

Blood

Eur J Cancer

J Biol Chem

Gynecol Oncol

The genetic analysis of ovarian cancer

Br J Cancer

Non-surgical aspect of ovarian cancer

Lancet

Glutathione and glutathione-dependent enzymes in ovarian adenocarcinoma cell lines derived from a patient before and after the onset of drug resistance: intrinsic differences and cell cycle effects

Carcinogenesis

In vitro platinum drug chemosensitivity of human cervical squamous cell carcinoma cell lines with intrinsic and acquired resistance to cisplatin

Br J Cancer

High resistance to cisplatin in human ovarian cancer cell lines is associated with marked increase of glutathione synthesis

Proc Natl Acad Sci USA

Insights into mechanisms of cisplatin resistance and potential for its clinical reversal

Pharmacotherapy

Potentiation of melphalan cytotoxicity in human ovarian cancer cell lines by glutathione depletion

Cancer Res

The relationship between glutathione, glutathione-S-transferase and cytotoxicity of platinum drugs and melphalan in eight human ovarian carcinoma cell lines

Br J Cancer

Regular Article
Cellular Glutathione Content, in Vitro Chemoresponse, and the Effect of BSO Modulation in Samples Derived from Patients with Advanced Ovarian Cancer