TRAIL mediates apoptosis in cancerous but not normal primary cultured cells of the human reproductive tract

Sadarangani, Anil; Kato, Sumie; Espinoza, Natalia; Lange, Soledad; Llados, Carmen; Espinosa, Marisol; Villalón, Manuel; Lipkowitz, Stanley; Cuello, Mauricio; Owen, Gareth I.

doi:10.1007/s10495-006-0713-5

Cited by 13 publications

(18 citation statements)

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“…As shown, micromolar concentrations of metformin do not statistically reduce the viability of either the A2780 or the SKOV3 ovarian cancer cell lines; however, at 48 hours, millimolar concentrations bring about cell death at each of the 3 millimolar concentrations tested. Loss of cell number and appearance of a cell death phenotype 20,21 is shown in representative images in Figure 1C. Metformin at 20 mmol/L was selected for further study, as this value is representative of the currently approved dosage in diabetes treatment and cell death was not observed at this concentration.…”

Section: Resultsmentioning

confidence: 99%

“…25,26 Previous publications from our laboratory have demonstrated that the loss of cell viability in this assay corresponds to ovarian cancer cell apoptosis. 20,21 Figures 2 and 3 demonstrate that the reduction in cell viability with chemotherapies tested in A2780 and SKOV3 is enhanced when cells were preexposed to metformin for 24 hours. Unsurprisingly, given that the 3 chemotherapies used have differing modes of action and that every cancer (and cell line) is unique, there were differing responses to each combination of metformin.…”

Section: Resultsmentioning

confidence: 99%

“…20,21 The cells were seeded at 50% density. Each experiment was repeated at least 3 times with 5 replicates per experiment.…”

Section: Measurement Of Cancer Cell Viabilitymentioning

confidence: 99%

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Metformin, at Concentrations Corresponding to the Treatment of Diabetes, Potentiates the Cytotoxic Effects of Carboplatin in Cultures of Ovarian Cancer Cells

et al. 2013

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The use of the type 2 diabetics drug metformin has been correlated with enhanced progression-free survival in ovarian cancer. The literature has speculated that this enhancement is due to the high concentration of metformin directly causing cancer cell death. However, this explanation does not fit with clinical data reporting that the women exposed to constant micromolar concentrations of metformin, as present in the treatment of diabetes, respond better to chemotherapy. Herein, our aim was to examine whether micromolar concentrations of metformin alone could bring about cancer cell death and whether micromolar metformin could increase the cytotoxic effect of commonly used chemotherapies in A2780 and SKOV3 cell lines and primary cultured cancer cells isolated from the peritoneal fluid of patients with advanced ovarian cancer. Our results in cell lines demonstrate that no significant loss of viability or change in cell cycle was observed with micromolar metformin alone; however, we observed cytotoxicity with micromolar metformin in combination with chemotherapy at concentrations where the chemotherapy alone produced no loss in viability. We demonstrate that previous exposure and maintenance of metformin in conjunction with carboplatin produces a synergistic enhancement in cytotoxicity of A2780 and SKOV3 cells (55% and 43%, respectively). Furthermore, in 5 (44%) of the 11 ovarian cancer primary cultures, micromolar metformin improved the cytotoxic response to carboplatin but not paclitaxel or doxorubicin. In conclusion, we present data that support the need for a clinical study to evaluate the adjuvant maintenance or prescription of currently approved doses of metformin during the chemotherapeutic treatment of ovarian cancer.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Metformin, at Concentrations Corresponding to the Treatment of Diabetes, Potentiates the Cytotoxic Effects of Carboplatin in Cultures of Ovarian Cancer Cells

et al. 2013

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“…Para este se utilizó MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3 carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, Cell Titer 96® (AQueous One Solution Cell Proliferation Assay, Promega, WI, EEUU). En este ensayo colorimétrico, la reducción del sustrato se correlaciona con la viabilidad o citotoxicidad en las células vivas 11 12,13,14 . Como control negativo de este ensayo se realizaron tratamientos con la droga ciclofosfamida, que requiere metabolización en el hígado para generar su compuesto activo, siendo inocuo para las células en cultivo.…”

Section: Metodologíaunclassified

Potencial herramienta en la personalización del tratamiento oncológico: Casos clínicos

Medina

et al. 2013

Rev. méd. Chile

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“…For example, combining ligation of death receptors with exposure to drugs increased tumor cell death in both drug resistant cell lines and primary ovarian carcinoma cells, even though these cells were not sensitive to death receptor ligation alone. Sadarangani et al (2007) have demonstrated that TRAIL at concentrations able to kill cancerous cells does not mediate apoptosis of normal cells. Similarly, Kato et al (2007), reported that the estrogen metabolite 2-methoxyoestradiol alone or in combination with TNF-related apoptosis-inducing ligand mediates apoptosis in cancerous but not healthy cells of the human endometrium thus suggesting that TRAIL may be an effective treatment for endometrial cancer.…”

Section: P Chaudhry and E Asselin: Therapeutic Resistance In Endometrmentioning

confidence: 99%

Resistance to chemotherapy and hormone therapy in endometrial cancer

Chaudhry¹,

Asselin²

2009

Endocrine-Related Cancer

109

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Endometrial cancer is the most common gynecological malignancy in developed countries and represents the eighth leading cause of cancer related death in women. The growing incidence of endometrial cancer leads scientists and oncologists to identify effective preventive measures and also molecular markers for diagnosis and prognosis. Chemotherapy and hormone therapy is the mainstay treatment option for advanced and recurrent endometrial cancer and response to therapy is one of the most important factor which favors prognosis and overall survival. In recent years, there have been major advances in the treatment of patients with endometrial cancer. Despite advances made in the treatment of this cancer, the overall survival of patients has not significantly improved because considerable number of patients harbor tumor refractory to these therapies and the majority of the initially responsive tumors become refractory to treatments. Therefore, determination of sensitivity/resistance is becoming increasingly important for individualization of endometrial cancer therapy. The aim of this review is to present the existing knowledge about the molecular markers that could play a crucial role in determining resistance to chemo-and hormone therapy. Extensive literature search for the cell signaling pathways and factors responsible for chemoresistance have been performed and reviewed. Several recent studies suggest that deregulations in the apoptotic pathways (such as p53, Fas/FasL, Bcl-2 family proteins, inhibitor of apoptosis proteins), survival pathways (PI3K/AKT, MAPK), hormone receptor signaling pathways (progesterone receptor), Cyclooxygenase-2 and Her-2 are considered as key factors involved in the onset and maintenance of therapeutic resistance, suggesting that resistance is a multi-factorial phenomenon.

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TRAIL mediates apoptosis in cancerous but not normal primary cultured cells of the human reproductive tract

Cited by 13 publications

References 0 publications

Metformin, at Concentrations Corresponding to the Treatment of Diabetes, Potentiates the Cytotoxic Effects of Carboplatin in Cultures of Ovarian Cancer Cells

Metformin, at Concentrations Corresponding to the Treatment of Diabetes, Potentiates the Cytotoxic Effects of Carboplatin in Cultures of Ovarian Cancer Cells

Potencial herramienta en la personalización del tratamiento oncológico: Casos clínicos

Resistance to chemotherapy and hormone therapy in endometrial cancer

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