Effects of Tamoxifen and Toremifene on ALDH1 and ALDH3 in Human Retinal Pigment Epithelial Cells and Rat Liver

Pappas, Periklis; Stephanou, Panayiotis; Sotiropoulou, Marianthi; Murphy, Carol; Salminen, Leena; Marselos, Marios

doi:10.1007/978-1-4615-4735-8_18

Cited by 3 publications

(3 citation statements)

References 17 publications

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“…For example, in liver class 2 mitochondrial ALDH is well expressed, whereas class 3 cytosolic ALDH is not present [8][9][10]. In the cornea and lens, there are high levels of class 3 cytosolic ALDH [11,12], the biological role of which could be important in the oxidation of peroxidic aldehydes, in UV-B photoprotection, and in preventing oxidative damage by free radical species [11].…”

Section: Introductionmentioning

confidence: 99%

Increase in class 2 aldehyde dehydrogenase expression by arachidonic acid in rat hepatoma cells

et al. 2001

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Aldehyde dehydrogenase (ALDH) is a family of several isoenzymes important in cell defence against both exogenous and endogenous aldehydes. Compared with normal hepatocytes, in rat hepatoma cells the following changes in the expression of ALDH occur: cytosolic class 3 ALDH expression appears and mitochondrial class 2 ALDH decreases. In parallel with these changes, a decrease in the polyunsaturated fatty acid content in membrane phospholipids occurs. In the present study we demonstrated that restoring the levels of arachidonic acid in 7777 and JM2 rat hepatoma cell lines to those seen in hepatocytes decreases hepatoma cell growth, and increases class 2 ALDH activity. This latter effect appears to be due to an increased gene transcription of class 2 ALDH. To account for this increase, we examined whether peroxisome-proliferator-activated receptors (PPARs) or lipid peroxidation were involved. We demonstrated a stimulation of PPAR expression, which is different in the two hepatoma cell lines: in the 7777 cell line, there was an increase in PPAR alpha expression, whereas PPAR gamma expression increased in JM2 cells. We also found increased lipid peroxidation, but this increase became evident at a later stage when class 2 ALDH expression had already increased. In conclusion, arachidonic acid added to the culture medium of hepatoma cell lines is able to partially restore the normal phenotype of class 2 ALDH, in addition to a decrease in cell growth.

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Section: Introductionmentioning

confidence: 99%

Increase in class 2 aldehyde dehydrogenase expression by arachidonic acid in rat hepatoma cells

et al. 2001

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“…Toremifene is a newer anticancer drug. It is closely related to tamoxifen but differs from it in the substitution of a chlorine atom for a hydrogen atom in the ethyl group (Pappas et al 1999). For advanced breast cancer and in an adjuvant setting, toremifene has been found to be as effective and well tolerated as tamoxifen (Holli et al 2000; Mäenpää et al 2000).…”

Section: Introductionmentioning

confidence: 99%

Ocular side‐effects in breast cancer patients treated with tamoxifen and toremifene: a randomized follow‐up study

Parkkari

Salminen

et al. 2003

Acta Ophthalmologica Scandinavica

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ABSTRACT.Purpose: 3Tamoxifen and toremifene are non-steroidal anti-oestrogens widely used in the treatment of advanced breast cancer and as adjuvant therapy following surgery in early stage disease. Tamoxifene has also been approved for use in reducing the incidence of breast cancer amongst high risk women. However, certain well documented adverse effects, mainly involving the reproductive organs, have been reported amongst users of both drugs. The aim of this study was to monitor the ocular side-effects of both of these commonly used anti-oestrogens. Methods: Sixty postmenopausal (age range 50-79 years) breast cancer patients were randomized into adjuvant tamoxifen or toremifene therapy groups for 3 years. Prior to commencement of medication, a thorough ocular examination was undertaken. The first follow-up visit took place after 6 months and the remaining three at 12-month intervals thereafter. Results: Sixteen patients had cataract at the first visit (seven in the tamoxifen group and nine in the toremifene group). Ten patients developed cataract during the study period (five in each group), giving annual cataract rates of 6.8% and 6.2% in the tamoxifen and toremifene groups, respectively. Three patients had macular crystals at the first visit (one in the tamoxifen group and two in the toremifene group). The crystals remained stable throughout the follow-up. Macular drusen were diagnosed in five patients at the first ophthalmological check-up (two in the tamoxifen and three in the toremifene group). Two patients in the toremifene group developed drusen maculopathy during follow-up visits. Yellowish spots in the macular area were found in one tamoxifen-treated patient at the second visit. At the final visit after 3.5 years' follow-up the spots had disappeared. No abnormal corneal findings or keratopathy were documented during the follow-up. Conclusion: We observed no serious ocular side-effects among the 60 breast cancer patients treated with tamoxifen or toremifene over a 3.5-year period.

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“…It is considered to be a component of the blood‐retina barrier with tight junctions between epithelial cells (Törnquist et al 1990) and it has a role in maintaining retinal glutamate homeostasis. In previous studies, retinal pigment epithelium has been found to be a sensitive target of antioestrogenic effects (Toimela et al 1998; Pappas et al 1999; Mannerström et al 2001; Engelke et al 2002; Mäenpää et al 2002). We have recently shown that antioestrogenic drugs inhibit glutamate uptake in cultured retinal pigment epithelal cells (Mäenpää et al 2002).…”

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confidence: 99%

Kinetics of Inhibition of Glutamate Uptake by Antioestrogens

Mäenpää

Saransaari

Tähti

2003

Pharmacology & Toxicology

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Abstract:The antioestrogens, tamoxifen and its more recent homologue toremifene, are used in the therapy of breast cancer. Tamoxifen has been reported to cause retinal changes as side effects. Both compounds inhibited glutamate uptake in retinal pigment epithelial cells, and the present study was conducted to clarify the mechanism of this inhibition. Retinal pigment epithelial cells are part of the blood-retina barrier, and their glutamate transporters are essential for retinal glutamate homeostasis. Glutamate uptake was investigated in human retinal pigment epithelial cell line D407 and in cultured pig retinal pigment epithelial cells using L-[ 3 H]glutamate as a tracer. The cells were exposed to 7.5 mM tamoxifen and toremifene. b-Hydroxyaspartate, a transportable inhibitor of glutamate transport, was used as a reference compound. In kinetic analyses, b-hydroxyaspartate increased the K m constant for glutamate transport. Tamoxifen and toremifene exhibited the same effect, which indicates that inhibition evoked by them is also competitive in nature. Both drugs were more effective in the human retinal pigment epithelial cell line than in the pig retinal pigment epithelial cells. The results show for the first time that the antioestrogens tamoxifen and toremifene could possibly hamper glutamate transport by replacing glutamate as the substrate.

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Effects of Tamoxifen and Toremifene on ALDH1 and ALDH3 in Human Retinal Pigment Epithelial Cells and Rat Liver

Cited by 3 publications

References 17 publications

Increase in class 2 aldehyde dehydrogenase expression by arachidonic acid in rat hepatoma cells

Increase in class 2 aldehyde dehydrogenase expression by arachidonic acid in rat hepatoma cells

Ocular side‐effects in breast cancer patients treated with tamoxifen and toremifene: a randomized follow‐up study

Kinetics of Inhibition of Glutamate Uptake by Antioestrogens

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