Malignant ascites increases the antioxidant ability of human ovarian (SKOV-3) and gastric adenocarcinoma (KATO-III) cells

Yang, Wenxuan; Toffa, S; Lohn, Jonathan W.G.; Seifalian, Alexander M.; Winslet, Marc C.

doi:10.1016/j.ygyno.2004.10.016

Cited by 16 publications

(10 citation statements)

References 37 publications

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“…GSH availability in control cells were demonstrated to decrease significantly over the duration of the experiment (p < 0.05). Similar reductions have been documented in another cell line 28 and are thought to be due to a significant reduction in nutrient availability with continual culture. Butyrate treatment significantly reduced the availability of GSH in Kato III cells after 24 hr, 48 hr (5 mM, 10 mM, p < 0.001) and 72 hr (10 mM, p < 0.05) compared to control values (Fig.…”

Section: Resultssupporting

confidence: 75%

Short-chain fatty acid modulation of apoptosis in the kato III human gastric carcinoma cell line

Matthews¹,

Howarth²,

Butler³

2007

Cancer Biology & Therapy

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The short-chain fatty acid (SCFA) butyrate is known to induce apoptosis in colon cancer cells in vitro and in vivo, however, its mode of action is poorly defined, whilst less is known regarding the effects of the SCFA propionate. This study investigated the potential for butyrate and propionate to alter cell viability, cell cycle regulation and intracellular protective mechanisms in a human gastric cancer cell line (Kato III). Kato III cells were incubated with butyrate or propionate for 24, 48 and 72 hr. At each time point, cells were assessed for the induction of apoptosis and cell cycle alterations using flow cytometry. Oxidative pentose pathway (OPP) activity and glutathione (GSH) availability were also measured as an index of intracellular protection. Butyrate and propionate differentially induced apoptosis and necrosis in Kato III cells and arrested cells in the G 2 -M phase. OPP activity was significantly increased by both SCFAs although butyrate induced a 10-fold greater increase than propionate. GSH availability was significantly decreased in Kato III cells by butyrate and propionate. These findings demonstrate that butyrate and propionate induce apoptosis and cell cycle alterations in Kato III gastric cancer cells. Moreover, the effects of butyrate were significantly greater than propionate. We propose that alterations to intracellular redox state and GSH availability play an important role in SCFA-mediated cell death in this cell type. The inclusion of butyrate and propionate as adjunctive cancer therapies has the potential to enhance the efficacy of current chemotherapeutics in the treatment of gastric cancer.

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Section: Resultssupporting

confidence: 75%

Short-chain fatty acid modulation of apoptosis in the kato III human gastric carcinoma cell line

Matthews¹,

Howarth²,

Butler³

2007

Cancer Biology & Therapy

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“…It is also well established that platinum analogues interact with sulfur-containing thiomolecules such as glutathione and metallothionein leading to its inactivation and subsequent failure from binding to DNA ( Siddik, 2003 ; Yang et al , 2006 ; Kelland, 2007 ). Also, studies in preclinical models and tumour samples suggest that elevated levels of glutathione or glutathione-related enzymes are associated with limited cisplatin efficacy ( Godwin et al , 1992 ; Yang et al , 2005 , 2006 ). Furthermore, glutathione as an antioxidant offers protection from ROS that are known to accumulate and induce apoptosis after radiotherapy and chemotherapeutic drug treatment ( Bragado et al , 2007 ; Choi et al , 2007 ).…”

Section: Discussionmentioning

confidence: 99%

PKM2 as a biomarker for chemosensitivity to front-line platinum-based chemotherapy in patients with metastatic non-small-cell lung cancer

et al. 2014

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Background:Tumour cells exclusively express the embryonic M2 isoform of pyruvate kinase (PKM2). PKM2 expression levels have been correlated with the effect of platinum compounds in cancer cell lines and xenograft models. The potential predictive role of PKM2 in patients with metastatic/advanced non-small-cell lung cancer (NSCLC) receiving platinum-based chemotherapy as first-line was investigated.Methods:Quantitative real-time PCR was used to assess the expression of PKM2 in tumour samples from 148 and 157 NSCLC patients in the training and the validation set, respectively. All patients received front-line platinum-based chemotherapy. PKM2 mRNA expression was also analysed in a control group of 85 NSCLC patients treated with non-platinum containing regimens.Results:In the training set, high PKM2 mRNA levels were associated with decreased progression-free survival (PFS; 4.9 months vs 6.4, P=0.006), overall survival (OS; 10.1 vs 17.0 months, P=0.01) and disease control rate (DCR; 57.7% vs 74.3% P=0.021) compared to patients with low PKM2 levels. In the validation set, high PKM2 mRNA levels were also associated with deceased PFS (3.7 vs 5.9 months, P=0.006), OS (8.3 vs 16.8 months, P=0.003) and DCR (57.7% vs 70.9% P=0.049) compared to those with low PKM2 mRNA levels. There was no correlation between the PKM2 mRNA levels and the PFS (5.6 vs 5.9, P=0.43) or the OS (9.8 vs 10.1, P=0.51) in the control group. Multivariate analysis revealed high PKM2 mRNA expression as an independent predictive factor for the poor patients' outcome.Conclusions:PKM2 expression may be a predictive biomarker of platinum sensitivity in advanced NSCLC patients treated with platinum-based chemotherapy.

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“…The obstruction of lymphatic vessels by tumor invasion is also thought to significantly contribute to malignant ascites (46). Cells released into the peritoneal cavity no longer have a vascular supply of oxygen and nutrients (47), which may explain the expression of EGFP observed in the cancer cells detected in ascites fluid. Yang et al ., have shown that ovarian and gastric tumor cells gained some degree of protection from oxidative and free radical derived damage in ascites (47).…”

Section: Discussionmentioning

confidence: 99%

“…Cells released into the peritoneal cavity no longer have a vascular supply of oxygen and nutrients (47), which may explain the expression of EGFP observed in the cancer cells detected in ascites fluid. Yang et al ., have shown that ovarian and gastric tumor cells gained some degree of protection from oxidative and free radical derived damage in ascites (47). Since hypoxic cancer cells are resistant to radiation and chemotherapy (48, 49), the presence of hypoxic cancer cells in ascites fluid and lymph nodes, may further contribute to poor treatment outcome in metastatic disease.…”

Section: Discussionmentioning

confidence: 99%

Noninvasive Multiparametric Imaging of Metastasis-Permissive Microenvironments in a Human Prostate Cancer Xenograft

et al. 2009

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Metastasis continues to be one of the major causes of mortality from prostate cancer. Because human malignant cell lines metastasize more readily from orthotopic sites than from heterotopic sites, to identify metastasis-permissive tumor microenvironments, we used noninvasive imaging to compare the in vivo vascular, metabolic, and physiologic characteristics of a human prostate cancer xenograft implanted orthotopically in the prostate or s.c. in the flank. Hypoxia was detected in these xenografts by placing an enhanced green fluorescence protein optical reporter under the control of a hypoxia response element. A multiparametric analysis of hypoxia, extracellular pH, vascularization, and metabolism provided a characterization of environments that are permissive for metastasis to occur. We found that orthotopic tumors, which metastasized more easily, were characterized by higher vascular volume, permeability, and total choline and a more acidic extracellular pH. Interestingly, metastatic deposits in the lymph nodes as well as cancer cells in ascites fluid were found to be hypoxic, explaining, in part, the refractory nature of metastatic disease. These results also provide the basis for clinically translatable noninvasive imaging markers for predicting metastatic risk in prostate cancer. [Cancer Res 2009;69(22):8822-9]

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Malignant ascites increases the antioxidant ability of human ovarian (SKOV-3) and gastric adenocarcinoma (KATO-III) cells

Cited by 16 publications

References 37 publications

Short-chain fatty acid modulation of apoptosis in the kato III human gastric carcinoma cell line

Short-chain fatty acid modulation of apoptosis in the kato III human gastric carcinoma cell line

PKM2 as a biomarker for chemosensitivity to front-line platinum-based chemotherapy in patients with metastatic non-small-cell lung cancer

Noninvasive Multiparametric Imaging of Metastasis-Permissive Microenvironments in a Human Prostate Cancer Xenograft

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