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The combination of glutamate receptor antagonist MK-801 with tamoxifen and its ...
Ribeiro, Mariana P. C.; Nunes-Correia, Isabel; Santos, Armanda E.; Custódio, José B. A.Recent reports suggest that N-methyl-d-aspartate receptor (NMDAR) blockade by MK-801 decreases tumor growth. Thus, we investigated whether other ionotropic glutamate receptor (iGluR) antagonists were also able to modulate the proliferation of melanoma cells. On the other hand, the antiestrogen tamoxifen (TAM) decreases the proliferation of melanoma cells, and is included in combined therapies for melanoma. As t...
The antiestrogen 4-hydroxytamoxifen protects against isotretinoin-induced perme...
Silva, Filomena S. G.; Ribeiro, Mariana P. C.; Santos, M. S.; Rocha-Pereira, Petronila; Santos-Silva, Alice; Custódio, José B. A.The combination of isotretinoin (13-cis-retinoic acid) with antiestrogens seems to be a promising strategy for cancer chemotherapy. The aim of the study was to evaluate the effects of isotretinoin alone or in combination with 4-hydroxytamoxifen (OHTAM) and with its prodrug tamoxifen (TAM), on the functions of rat liver mitochondria, i.e., mitochondrial permeability transition (MPT), bioenergetic functions and a...
Comparative effects of three 1,4-dihydropyridine derivatives [OSI-1210, OSI-121...
Fernandes, Maria A. S.; Pereira, Susana P. S.; Jurado, Amália S.; Custódio, José B. A.; Santos, Maria S.; Moreno, António J. M.; Duburs, GunarsThe 1,4-dihydropyridines OSI-1210, OSI-1211 (etaftoron), and OSI-3802 are compounds with similar chemical structure. They differ by the length of the alkoxyl chain in positions 3 and 5 of the dihydropyridine (DHP) ring and by their pharmacological action characteristics. However, as far as we know, a clear relationship between the effects of these compounds and the length of the alkoxyl chain in positions 3 and...
Estradiol affects liver mitochondrial function in ovariectomized and tamoxifen-...
Moreira, Paula I.; Custódio, José B.A.; Nunes, Elsa; Moreno, António; Seiça, Raquel; Oliveira, Catarina R.; Santos, Maria S.Given the tremendous importance of mitochondria to basic cellular functions as well as the critical role of mitochondrial impairment in a vast number of disorders, a compelling question is whether 17[beta]-estradiol (E2) modulates mitochondrial function. To answer this question we exposed isolated liver mitochondria to E2. Three groups of rat females were used: control, ovariectomized and ovariectomized treated...
Estradiol affects liver mitochondrial function in ovariectomized and tamoxifen-...
Moreira, Paula I.; Custódio, José B.A.; Nunes, Elsa; Moreno, António; Seiça, Raquel; Oliveira, Catarina R.; Santos, Maria S.Given the tremendous importance of mitochondria to basic cellular functions as well as the critical role of mitochondrial impairment in a vast number of disorders, a compelling question is whether 17[beta]-estradiol (E2) modulates mitochondrial function. To answer this question we exposed isolated liver mitochondria to E2. Three groups of rat females were used: control, ovariectomized and ovariectomized treated...
Tetrandrine concentrations not affecting oxidative phosphorylation protect rat ...
Fernandes, Maria A. S.; Custódio, José B. A.; Santos, Maria S.; Moreno, António J. M.; Vicente, Joaquim A. F.The effects of tetrandrine (6,6', 7,12-tetramethoxy-2, 2'-dimethyl-berbaman) on the mitochondrial function were assessed on oxidative stress, mitochondrial permeability transition (MPT), and bioenergetics of rat liver mitochondria. At concentrations lower than 100 nmol/mg protein, tetrandrine decreased the hydrogen peroxide formation, the extent of lipid peroxidation, the susceptibility to Ca2+-induced opening ...
Protection of tamoxifen against oxidation of mitochondrial thiols and NAD(P)H u...
Cardoso, Carla M. P.; Almeida, Leonor M.; Custódio, José B. A.The effects of tamoxifen (TAM) were studied on the mitochondrial permeability transition (MPT) induced by the prooxidant tert-butyl hydroperoxide (t-BuOOH) or the thiol cross-linker phenylarsine oxide (PhAsO), in the presence of Ca2+, in order to clarify the mechanisms involved in the MPT inhibition by this drug. The combination of Ca2+ with t-BuOOH or PhAsO induces mitochondrial swelling and depolarization of ...
Comparison of the changes in adenine nucleotides of rat liver mitochondria indu...
Cardoso, Carla M. P.; Moreno, António J. M.; Almeida, Leonor M.; Custódio, José B. A.The antiestrogen tamoxifen (TAM) inhibits the growth of different estrogen receptor (ER)-negative cells. Recently, multiple effects of TAM on mitochondrial bioenergetic functions have been pointed to explain its ER-independent cell death mechanisms. We have shown that TAM and its major active metabolite 4-hydroxytamoxifen (OHTAM) induce depolarization of the mitochondrial membrane potential ([Delta][Psi]) and u...
4-Hydroxytamoxifen induces slight uncoupling of mitochondrial oxidative phospho...
Cardoso, Carla M. P.; Moreno, António J. M.; Almeida, Leonor M.; Custódio, José B. A.The use of tamoxifen (TAM) has been questioned on the chemotherapy and chemoprevention of breast cancer due to several estrogen receptor-independent cytotoxic effects. As an alternative, its more active metabolite 4-hydroxytamoxifen (OHTAM) has been proposed with presumed lower side effects. In this work, the potential OHTAM toxicity on rat liver mitochondrial bioenergetics in relation to the multiple deleterio...
4-Hydroxytamoxifen is a potent inhibitor of the mitochondrial permeability tran...
Cardoso, Carla M. P.; Almeida, Leonor M.; Custódio, José B. A.The effects of 4-hydroxytamoxifen (OHTAM), the major active metabolite of the antiestrogen tamoxifen used in the breast cancer therapy, were studied on the mitochondrial permeability transition (MPT) and bioenergetic functions of mitochondria to evaluate the mechanisms underlying the cell death and toxic effects. The MPT was induced in vitro by incubating rat liver mitochondria with 1 mM inorganic phosphate plu...
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