Specific Expression of Glutathione S-transferase Pi Forms in (Pre)neoplastic Tissues: Their Properties and Functions.

Sato, Kei; Satoh, Keisuke; Tsuchida, Shigeki; Hatayama, Ichiro; Shen, Hongxie; Yokoyama, Yoshihiko; Yamada, Yuichi; Tamai, Katsuto

doi:10.1620/tjem.168.97

Cited by 15 publications

(10 citation statements)

References 10 publications

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“…GSTP1-1 is overexpressed in various cancers, including gastric cancer, lung cancer, ovarian cancer, and precancerous lesions 35–38 . Therefore, our data suggest that a fluorogenic probe targeting GSTP1-1 for molecular imaging would also be very useful for the early diagnosis and/or evaluation of chemopreventive agents for these types of cancers.…”

Section: Discussionmentioning

confidence: 99%

Molecular imaging of aberrant crypt foci in the human colon targeting glutathione S-transferase P1-1

Muguruma

Okamoto

Nakagawa

et al. 2017

Sci Rep

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Aberrant crypt foci (ACF), the earliest precursor lesion of colorectal cancers (CRCs), are a good surrogate marker for CRC risk stratification and chemoprevention. However, the conventional ACF detection method with dye-spraying by magnifying colonoscopy is labor- and skill-intensive. We sought to identify rat and human ACF using a fluorescent imaging technique that targets a molecule specific for ACF. We found that glutathione S-transferase (GST) P1-1 was overexpressed in ACF tissues in a screening experiment. We then synthesized the fluorogenic probe, DNAT-Me, which is fluorescently quenched but is activated by GSTP1-1. A CRC cell line incubated with DNAT-Me showed strong fluorescence in the cytosol. Fluorescence intensities correlated significantly with GST activities in cancer cell lines. When we sprayed DNAT-Me onto colorectal mucosa excised from azoxymethane-treated rats and surgically resected from CRC patients, ACF with strong fluorescent signals were clearly observed. The ACF number determined by postoperative DNAT-Me imaging was almost identical to that determined by preoperative methylene blue staining. The signal-to-noise ratio for ACF in DNAT-Me images was significantly higher than that in methylene blue staining. Thus, we sensitively visualized ACF on rat and human colorectal mucosa by using a GST-activated fluorogenic probe without dye-spraying and magnifying colonoscopy.

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Section: Discussionmentioning

confidence: 99%

Molecular imaging of aberrant crypt foci in the human colon targeting glutathione S-transferase P1-1

Muguruma

Okamoto

Nakagawa

et al. 2017

Sci Rep

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“…1), we found that the induction of γ-H2AX was reduced when the intracellular levels of glutathione were depleted by BSO. Together the above results further justify the rationale for using brostallicin in tumors with high glutathione levels, which is a relatively common feature of cancer cells especially after prior chemotherapy (7, 18–20, 23–25, 44). …”

Section: Discussionmentioning

confidence: 54%

“…Indeed, the DNA damaging activity of brostallicin is enhanced by high levels of glutathione, which is a hallmark of drug-resistant tumor cells (7, 18, 21–25). We also show for the first time that brostallicin selectively damages and blocks replicating DNA within replication factories.…”

Section: Discussionmentioning

confidence: 99%

“…This is in contrast with classical DNA alkylating agents that tend to be inactivated by elevated glutathione, which is a common feature of cancer cells (19, 20). Thus, the over-expression of glutathione and glutathione-S-transferase in tumor cells (21–25), confers a potential selectivity of brostallicin toward cancer cells, and sets it apart from other DNA alkylating agents. The proposed molecular mechanism for the activation of brostallicin by glutathione involves a reaction of the α-bromoacrylic moiety of brostallicin with glutathione, which is catalyzed by glutathione-S-transferase, to form a highly reactive glutathione-brostallicin complex able to alkylate the exocyclic N2-position of guanines in the minor groove of DNA (7, 18) (Fig.…”

Section: Introductionmentioning

confidence: 99%

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Induction of glutathione-dependent DNA double-strand breaks by the novel anticancer drug brostallicin

Guirouilh‐Barbat

Zhang

Pommier

2009

Molecular Cancer Therapeutics

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Brostallicin is a DNA minor groove binder in phase II clinical trials. Here, we show that brostallicin induces γ-H2AX nuclear foci that colocalize with 53BP1 and are dependent on glutathione, as shown by inhibition of those γ-H2AX foci by L-buthionine sulfoximine. To differentiate brostallicin from the clinically approved minor groove binder trabectedin (ecteinascidin 743), we tested whether the brostallicin-induced γ-H2AX and antiproliferative responses were dependent on nucleotide excision repair and found that, unlike trabectedin, they are not. Additionally, brostallicin retained activity in the trabectedin-resistant HCT116-ER5 cell line. Induction of γ-H2AX foci by brostallicin was partially dependent on the repair nuclease Mre11. Pretreatment with aphidicolin partially reduced brostallicin-induced γ-H2AX foci, suggesting that brostallicin induces both replication-associated and replicationindependent DNA damage. Replication-associated DNA damage was further shown by the colocalization of γ-H2AX foci with replication foci and by the rapid inhibition of DNA synthesis and accumulation of cells in S phase in response to brostallicin. In addition, brostallicin was able to induce lower intensity γ-H2AX foci in human circulating lymphocytes. Together, our results indicate that brostallicin induces DNA double-strand breaks and suggest γ-H2AX as a pharmacodynamic biomarker for brostallicin. [Mol Cancer Ther 2009;8(7):1985-94]

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“…Previous studies have demonstrated that abnormal tumor suppressor gene promoter methylation could inactivate the corresponding genes and thus promote tumor development and progression (7,8). The GSTP1 gene is a very important DNA damage repair gene that can inhibit the effects of cytotoxic agents and carcinogens and is regarded as a tumor suppressor gene (9). Previous studies have also demonstrated that hypermethylation of the CpG islands in the GSTP1 gene promoter is involved in the development and progression of multiple tumors, and thus could be used as a promising biomarker to help early screening, diagnosis, and patient prognosis (10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Demethylation effects of elemene on the GSTP1 gene in HCC cell line QGY7703

Jiang

Zhu

et al. 2016

Oncology Letters

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Abstract. The present study aimed to investigate elemene's effects on cell proliferation, apoptosis, and the cell cycle in the hepatocellular carcinoma (HCC) cell line, QYG7703, and to investigate GSTP1 gene methylation change in QGY7703 cells after being treated with elemene to explore whether elemene reversed the abnormal GSTP1 gene methylation. QGY7703 cells were treated with different elemene concentrations. Cell proliferation was measured with MTT assay, cell apoptosis and cell cycle were analyzed by flow cytometry, and GSTP1 gene methylation was analyzed by methlation-specific polymerase chain reaction. The cells' apoptotic rate increased dose-dependently with elemene concentration, and the difference was statistically significant (P<0.05). Elemene treatment arrested the cells in S phase, and thus the percentage of cells in G1 phase decreased while the cells in S phase increased dose-dependently, and the difference was statistically significant compared to the control group (P<0.05). All QGY7703 cells were identified to contain GSTP1 gene methylation before being treated with elemene and the methylation state decreased after treatment. In the present study, elemene induced cell apoptosis, inhibited the cell cycle, and reversed GSTP1 gene methylation in QGY7703 cells.

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Specific Expression of Glutathione S-transferase Pi Forms in (Pre)neoplastic Tissues: Their Properties and Functions.

Cited by 15 publications

References 10 publications

Molecular imaging of aberrant crypt foci in the human colon targeting glutathione S-transferase P1-1

Molecular imaging of aberrant crypt foci in the human colon targeting glutathione S-transferase P1-1

Induction of glutathione-dependent DNA double-strand breaks by the novel anticancer drug brostallicin

Demethylation effects of elemene on the GSTP1 gene in HCC cell line QGY7703

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