Glutathione‐S‐transferase enhances proliferation‐migration and protects against shikonin‐induced cell death in breast cancer cells

Abstract

Glutathione-S-transferase (GST) is a cytoplasmic protein responsible for detoxification, but the effect of the enzyme on cell biological events, including proliferation and migration, has never been reported. Thus, we evaluated the detoxification effect of in vitro-applied GST on cancer cell proliferation and migration. Assays for proliferation and migration of human breast cancer cells in the presence of GST were carried out. Binding of GST on the surface of the cancer cells was studied by flow cytometry. Detoxification through GST pathway was studied in the presence of shikonin. The effective dosage of GST in enhancement of cell proliferation was 10-50 nM, and the cell migration could be significantly enhanced after 6 hours in the presence of 2-50 nM GST. Therefore, overall cell proliferation and migration could be enhanced in the presence of 10nM or greater concentration of GST, and 15 μM shikonin-induced toxification of the cancer cells could be neutralized by 1.0 μM GST. Flow cytometry showed that GST directly bound to the surface of the cancer cells, and this was confirmed by fluorescence confocal microscopic observation. It is concluded that human class π-GST enhances proliferation and migration of human breast cancer cells by means of direct binding to the cell surface and maintaining cell viability by detoxification.

Infection of Schistosomiasis japanicum is likely to enhance proliferation and migration of human breast cancer cells: mechanism of action of differential expression of MMP2 and MMP9

“…Migration assays were carried out according to our recent report [25] for the different concentrations of sjGST in BD Falcon 24-well culture plate (BD Biosciences). The cells were seeded in the plate wells with or without 1 mm tape stuck in the middle and grown to 100% confluent.…”

High serum iron and zinc decrease glutathione S-transferase among women with breast cancer

“…Glutathione-S-transferase (GST) is a cytoplasmic protein responsible for detoxification. The study by He et al (18) showed that cell proliferation and migration could be enhanced in greater concentrations of GST, where GST directly bound to the surface of the cancer cells. Glutathione-S-transferase activities were higher in the breast tumor than in the normal cytosolic fractions.…”

Regulatory expression of MMP‐8/MMP‐9 and inhibition of proliferation, migration and invasion in human lung cancer A549 cells in the presence of HGF variants

“…The A549 human lung adenocarcinoma cells obtained from the American Type culture collection (ATCC CCL‐185, Manassas, VI, USA) were maintained in L‐15 media containing 10% fetal bovine serum, 50 g/L penicillin, and 100 mg/L streptomycin (Hyclone Laboratories, Inc., Logan, UT, USA) at 37°C in a humidified chamber with replacement of the media every 2 days as described [43,44] with modifications.…”

“…The entire process was carried out according to the protocol as reported [14,43], with some modifications in a predetermined period of 8 days where approximately 1000 cells were incubated in the 96‐well plates with L‐15 media, containing 10% fetal bovine serum at 37°C in an incubation chamber, with respect to HGF variant proteins ( NK1 , NK2 , NK3 , and NK4 ), GST at 4 nM. At each interval of 2 days, fresh media and proteins were added and plates were collected at the end of 2 days, 4 days, 6 days, and 8 days.…”