2005
DOI: 10.1007/s00280-004-0920-0 View full text |Buy / Rent full text
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Abstract: The overexpression of gsto1 in normally chemoresistant and radioresistant LY-ar cells renders them vulnerable to the cytotoxic effects of As(2)O(3), despite the 30-fold overexpression of the survival factor bcl-2. Gsto1 and its human homolog, GSTO1, may serve as a marker for arsenic sensitivity, particularly in cells that are resistant to other chemotherapeutic agents.

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“…Zhao et al, demonstrated As 2 O 3 significantly decreased the expression of GST-π and decreased expression of Topo-II, which indicated these MDR-related enzymes may be contributed to the partial reverse of MDR induced by As 2 O 3 in K563/A02 cells [ 20 ]. Another line of evidence suggested that As 2 O 3 eliminated chemo-resistance in murine B-cell lymphoma via the overexpression of p28 [ 21 ]. Recent study also showed that As 2 O 3 inhibited the expression of Bcl-2 and Bcl-xL, and increased the expression of Bax in HCC cells, which in turn enhances sorafenib-induced apoptosis in HCC [ 23 ].…”
Section: Discussionmentioning
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“…Zhao et al, demonstrated As 2 O 3 significantly decreased the expression of GST-π and decreased expression of Topo-II, which indicated these MDR-related enzymes may be contributed to the partial reverse of MDR induced by As 2 O 3 in K563/A02 cells [ 20 ]. Another line of evidence suggested that As 2 O 3 eliminated chemo-resistance in murine B-cell lymphoma via the overexpression of p28 [ 21 ]. Recent study also showed that As 2 O 3 inhibited the expression of Bcl-2 and Bcl-xL, and increased the expression of Bax in HCC cells, which in turn enhances sorafenib-induced apoptosis in HCC [ 23 ].…”
Section: Discussionmentioning
“…Although the detailed molecular mechanisms of arsenic trioxide are not clarified, results in various studies have showed that As 2 O 3 involves in induction of apoptosis, partial cellular differentiation, degradation of specific APL fusion transcripts, anti-proliferation, generation of reactive oxygen species [ 18 , 19 ]. Recent studies also demonstrated that As 2 O 3 reduces drug resistance to adriamycin in leukemic K562/A02 cells via multiple mechanisms [ 20 ], and arsenic trioxide eliminates the differential chemo-resistance in B cell lymphoma cells via the overexpression of p28 [ 21 ]. Another study showed that As 2 O 3 re-sensitized cells to 5-fluorouracil (5-FU) in 5-FU-resistant colorectal cancer cell line via suppression of thymidylate synthase [ 22 ].…”
Section: Introductionmentioning
“…It was found that wild-type GSTO1 (A140/A140) correlated with advanced stage breast cancer. Recently, a study demonstrated that mouse GSTO1 overexpressed in a lymphoma cell line with resistance to radiation and chemotherapeutics 17 . Since GSTO1 appears to be involved in drug and xenobiotic metabolism, it would be of great interest to investigate further whether resistance to radiation or chemotherapy occurs in carriers of wild-type GSTO1, particularly those with advanced stage breast cancer.…”
Section: Discussionmentioning
“…GSTP1-1 contributes to resistance against cytostatic drugs and apoptosis (Johansson et al, 2000). Both hGSTO1-1 and GSTO2-2 have been documented to induce inflammation and to contribute to the pathogenesis of Alzheimer's disease and apoptosis (Ogru et al, 2004;Giri et al, 2005;Wang et al, 2005). Thus, despite the marked differences between hGSTO1-1 and GSTP1-1, we examined hGSTO1-1 as a possible target for inhibition by α-tocopherol.…”
Section: Introductionmentioning