Development of Mechanisms of Protection Against Oxidative Stress in Doxorubicin-Resistant Rat Tumoral Cells in Culture

Benchekroun, Mohamed Nabil; Catroux, P; Montaudon, Danièle; Robert, Jacques

doi:10.3109/10715769009109676

Cited by 13 publications

(6 citation statements)

References 19 publications

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“…Bcl-2 and members of its family are powerful antioxidant agents and may be augmented in MDR cell lines. Similarly, an increased expression of antioxidant enzymes such as glutathione peroxidase or high levels of scavengers such as a-tocopherol present in the cellular membrane have been described (Benchekroun et al 1990, Mazzanti et al 1995. Lucena 1 cells are more resistant to H 2 O 2 and to ultraviolet-A radiation (UVA) than the parental K562 cell line.…”

Section: Resistance To Oxidative Stressmentioning

confidence: 99%

“…A number of MDR cells lines were shown to be more resistant to lipid peroxidation than their parental lines and different mechanisms have been attributed to explain this increased resistance (Benchekroun et al 1990, Hoban et al 1992, Hill et al 1995, Lenehan et al 1995, Mazzanti et al 1995, Kühl et al 1997. Bcl-2 and members of its family are powerful antioxidant agents and may be augmented in MDR cell lines.…”

Section: Resistance To Oxidative Stressmentioning

confidence: 99%

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Multidrug resistance in tumour cells: characterisation of the multidrug resistant cell line K562-Lucena 1

Rumjanek

Trindade

Wagner-Souza

et al. 2001

An. Acad. Bras. Ciênc.

115

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Multidrug resistance to chemotherapy is a major obstacle in the treatment of cancer patients. The best characterised mechanism responsible for multidrug resistance involves the expression of the MDR-1 gene product, P-glycoprotein. However, the resistance process is multifactorial. Studies of multidrug resistance mechanisms have relied on the analysis of cancer cell lines that have been selected and present cross-reactivity to a broad range of anticancer agents. This work characterises a multidrug resistant cell line, originally selected for resistance to the Vinca alkaloid vincristine and derived from the human erythroleukaemia cell K562. This cell line, named Lucena 1, overexpresses P-glycoprotein and have its resistance reversed by the chemosensitisers verapamil, trifluoperazine and cyclosporins A, D and G. Furthermore, we demonstrated that methylene blue was capable of partially reversing the resistance in this cell line. On the contrary, the use of 5-fluorouracil increased the resistance of Lucena 1. In addition to chemotherapics, Lucena 1 cells were resistant to ultraviolet A radiation and hydrogen peroxide and failed to mobilise intracellular calcium when thapsigargin was used. Changes in the cytoskeleton of this cell line were also observed.

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Section: Resistance To Oxidative Stressmentioning

confidence: 99%

Section: Resistance To Oxidative Stressmentioning

confidence: 99%

Multidrug resistance in tumour cells: characterisation of the multidrug resistant cell line K562-Lucena 1

Rumjanek

Trindade

Wagner-Souza

et al. 2001

An. Acad. Bras. Ciênc.

115

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“…We have recently shown that glutathione peroxidase activities were enhanced in doxorubicin-resistant tumor cells in culture, whereas total glutathione S-transferase activities remained unchanged [24]. In an attempt to show if this enhancement has a role to play in detoxifying the peroxides formed from the redox cycling of doxorubicin, we have developed a technique for the evaluation of these peroxides in cultured cells exposed to the drug [25].…”

mentioning

confidence: 99%

Doxorubicin‐induced lipid peroxidation and glutathione peroxidase activity in tumor cell lines selected for resistance to doxorubicin

Benchekroun

Pourquier

Schott

et al. 1993

European Journal of Biochemistry

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Doxorubicin‐induced lipid peroxidation was evaluated in four human or murine cell strains in culture and in their doxorubicin‐resistant variants, by the quantification of malondialdehyde produced after a 2‐h incubation of cells with the drug. Significantly increased malondialdehyde levels were obtained 24 h after doxorubicin treatment in three of the wild‐type cell lines with doses as low as 0.05–0.1 μg/ml, which is within an order of magnitude of the concentration of the drug which inhibits cell growth by 50%. This production of malondialdehyde was abolished in two doxorubicinresistant strains, even with high doses of drug (100–300 μg/ml), but was maintained in the third resistant line. No malondialdehyde production was observed in the fourth cell line, sensitive or resistant. It is remarkable that an enhancement of selenium‐dependent and non‐selenium‐dependent glutathione peroxidase activities was exhibited during the acquisition of resistance to doxorubicin in the two first lines, but not in the third, whereas a constitutively high non‐selenium‐dependent glutathione peroxidase activity existed in the doxorubicin‐sensitive and doxorubicin‐resistant variants of the fourth cell line. Gene expression of selenium‐dependent glutathione peroxidase and of glutathione S‐transferase π, which is known partially to bear a non‐selenium‐dependent glutathione peroxidase activity, were correlated with the corresponding enzyme activities. It appears, therefore, that the already known enhancement of glutathione peroxidase activity and expression in doxorubicin‐resistant cell lines has a quantifiable consequence upon doxorubicin‐induced lipid peroxidation and may have consequences in the mechanism of resistance to this drug.

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“…Doxorubicin is well known to exert oxidative stress to cells (41). The cytotoxicity of RCC cells to doxorubicin combined with sorafenib was investigated.…”

Section: -------------------------------------------------mentioning

confidence: 99%

Sorafenib with doxorubicin augments cytotoxicity to renal cell cancer through PERK inhibition

Shiota

Eto²,

Yokomizo

et al. 2010

Int J Oncol

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Abstract. Although cytokine therapy involving interleukin-2 or interferon-· has been employed for metastatic renal cell cancer (RCC) treatment, these therapies yielded limited response and benefit. Recently, several molecular-targeted agents have become available, and one newly developed anti-RCC agent, sorafenib , is known to target multiple kinases. In this study, sorafenib was found to inhibit phosphorylation of the eukaryotic initiation factor-2· (eIF2·) and induce cell cycle arrest at G2/M phase and increase cell death. One of eIF2· kinases, PERK was responsible for eIF2· phosphorylation in RCC cells and PERK knockdown induced cell death similar to sorafenib treatment. The efficiency of sorafenib treatment correlated with phosphorylation level of eIF2· and nuclear Nrf2 expression level in eight RCC cell lines. Furthermore, sorafenib made Caki-1 and 786-O cells, but not ACHN cells sensitive to oxidative stress exerted by both hydrogen peroxide and doxorubicin. In addition, PERK knockdown sensitized Caki-1 and 786-O cells, but not ACHN cells to oxidative stress. In conclusion, levels of phospho-eIF2· and nuclear Nrf2 expression level in RCC might be a predictor of outcome in sorafenib treatment. In addition, PERK inhibition as well as sorafenib plus doxorubicin might be a promising therapeutic approach for RCC characterized by high levels of phosphorylatedeIF2· and nuclear Nrf2.

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Development of Mechanisms of Protection Against Oxidative Stress in Doxorubicin-Resistant Rat Tumoral Cells in Culture

Cited by 13 publications

References 19 publications

Multidrug resistance in tumour cells: characterisation of the multidrug resistant cell line K562-Lucena 1

Multidrug resistance in tumour cells: characterisation of the multidrug resistant cell line K562-Lucena 1

Doxorubicin‐induced lipid peroxidation and glutathione peroxidase activity in tumor cell lines selected for resistance to doxorubicin

Sorafenib with doxorubicin augments cytotoxicity to renal cell cancer through PERK inhibition

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