Dissimilar action of tamoxifen and 4-hydroxytamoxifen on phosphatidylcholine model membranes

Ortiz, Julia; Aranda, Francisco J.; Teruel, José A.; Ortíz, Antonio Gómez

doi:10.1016/j.bpc.2021.106681

Cited by 3 publications

(10 citation statements)

References 52 publications

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“…Analysis of mass density profiles ( Figure 8 ) showed that TMX could be found all along the whole lipid phase, but was mainly located at the center of the bilayer, in agreement with previous data on fluid DPPC membranes [ 11 ]. No relevant differences were found between the various compositions under study.…”

Section: Resultssupporting

confidence: 89%

“…Accordingly, a number of experimental works have addressed the study of the interaction of TMX and HTMX with biological membranes. TMX has been shown to widen and shift the gel to liquid–crystalline phase transition of PC model membranes [ 6 , 7 , 8 , 9 , 10 , 11 ], to alter membrane fluidity [ 7 , 54 ], to induce stomatocyte formation in human erythrocytes [ 55 ], and was briefly reported to permeabilize model phospholipid vesicles [ 9 , 10 , 11 ].…”

Section: Discussionmentioning

confidence: 99%

“…Multilamellar vesicles for DSC measurements were prepared by the dry film hydration method, essentially as described previously [ 11 ]. Briefly, the appropriate amounts of phospholipids and TMX were mixed in chloroform, and the organic solvent was gently evaporated using dry N 2 , to obtain a thin film at the bottom of a glass tube.…”

Section: Methodsmentioning

confidence: 99%

“…Nevertheless, in addition to receptor binding, the preferential partitioning of TMX and HTMX into cellular membranes, due to their highly hydrophobic character, results in additional alterations of membrane structure and function [ 5 ]. The interactions of TMX and HTMX with phosphatidylcholine (PC) model membranes have been studied in a number of works [ 6 , 7 , 8 , 9 , 10 , 11 , 12 ], providing details on their effects on membrane fluidity, order, hydration, and other physicochemical parameters. In addition, one recent work has reported on the interactions of TMX and HTMX with a phosphatidylethanolamine (PE) system, the second most important phospholipid in biological membranes [ 13 ], showing that these two drugs facilitate the formation of the inverted hexagonalH II phase [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

“…Many works have described membrane permeabilization in model vesicles or liposome systems of various compositions, induced by different compounds, among which cytotoxic amphipathic helices [ 17 ], apoptotic peptides [ 18 ], and bacterial glycolipids [ 19 , 20 ], or lipopeptides [ 21 ] can be cited. Within this context, the hemolytic activity of TMX has been described [ 22 ], and it has also been briefly reported that TMX can permeabilize model phospholipid vesicles [ 9 , 10 , 11 ]. Thus, it seems evident that the interaction of TMX with biological membranes not only alters their physicochemical properties, but also compromises their barrier function, an issue which deserves more profound study.…”

Section: Introductionmentioning

confidence: 99%

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On the Mechanism of Membrane Permeabilization by Tamoxifen and 4-Hydroxytamoxifen

et al. 2023

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Tamoxifen (TMX), commonly used in complementary therapy for breast cancer, also displays known effects on the structure and function of biological membranes. This work presents an experimental and simulation study on the permeabilization of model phospholipid membranes by TMX and its derivative 4-hydroxytamoxifen (HTMX). TMX induces rapid and extensive vesicle contents leakage in phosphatidylcholine (PC) liposomes, with the effect of HTMX being much weaker. Fitting of the leakage curves for TMX, yields two rate constants, corresponding to a fast and a slow process, whereas in the case of HTMX, only the slow process takes place. Interestingly, incorporation of phosphatidylglycerol (PG) or phosphatidylethanolamine (PE) protects PC membranes from TMX-induced permeabilization. Fourier-transform infrared spectroscopy (FTIR) shows that, in the presence of TMX there is a shift in the νCH2 band frequency, corresponding to an increase in gauche conformers, and a shift in the νC=O band frequency, indicating a dehydration of the polar region. A preferential association of TMX with PC, in mixed PC/PE systems, is observed by differential scanning calorimetry. Molecular dynamics (MD) simulations support the experimental results, and provide feasible explanations to the protecting effect of PG and PE. These findings add new information to explain the various mechanisms of the anticancer actions of TMX, not related to the estrogen receptor, and potential side effects of this drug.

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Section: Resultssupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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On the Mechanism of Membrane Permeabilization by Tamoxifen and 4-Hydroxytamoxifen

et al. 2023

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Influence of CYP2D6 and its polymorphic forms on the metabolism of tamoxifen in therapy of luminal forms of breast cancer

Yurchenko,

Shkarupa,

Kakarkin

et al. 2024

Rep. of Vinnytsia Nation. Med. Univ.

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Annotation. Tamoxifen belongs to the group of selective estrogen receptor modulators (SERM) and is metabolized by the detoxification system of xenobiotics, and the phenomenon of metabolic activation can be observed at the first stage. CYP2D6 also directly participates in this process, the analysis of polymorphic forms of which can influence the prediction of the effectiveness and toxicity of tamoxifen in the treatment of luminal forms of breast cancer, which is of great importance considering the duration of therapy with this drug. The aim – to analyze scientific literature data on the effect of CYP2D6 and its polymorphs on the metabolism of tamoxifen in the treatment of luminal forms of breast cancer. A retrospective analysis of the literature of scientific databases Scopus, Web of Science, PubMed., MedLines for 2013-2023 was carried out. It is established that CYP2D6 can be considered a predictor of treatment effectiveness only in patients with breast cancer (ER+) who are postmenopausal and receive 20 mg of tamoxifen per day for 5 years and do not have hepatotoxic conditions and CYP2D6 inhibition phenomena, which determines the expediency of genotyping CYP2D6 polymorphic variants in such a group. Long-term therapy with tamoxifen can be complicated by the development of secondary endometrial cancer. Undesirable effects of tamoxifen may also depend on the activity of CYP2D6. Thus, in slow metabolizers, for example, carriers of CYP2D6*3/*4 and CYP2D6*6/*6, a statistically significant increase in the frequency of cases of endometrial hyperplasia was observed. In addition, polymorphisms of other enzymes of the biotransformation system of xenobiotics that participate in both the activation and deactivation of tamoxifen and its metabolites, both the first (CYP3A4, CYP3A5, CYP2B6, CYP2C9, CYP2C19 and CYP2D6) and the second phase (SULT and UGT), remain a promising direction for study. The study of the consequences of the phenomena of iatrogenic cholestasis and drug interactions at the level of CYP2D6, which may affect the metabolism of tamoxifen, also requires a detailed study, taking into account the intensive pharmacotherapy of BC.

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Tooth loss in breast cancer patients: A comparison between tamoxifen-treated and non-treated patients

Julca-Baltazar,

Asmat-Abanto,

Pantoja-Lázaro

et al. 2024

Med Oral

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Background Tooth loss (TL) affects quality of life and general health. The literature suggesting that tamoxifen treatment in patients with breast cancer (BC) could be associated with alterations in oral health, increasing the risk of TL, is still scarce. This work aimed to determine the relationship between TL and tamoxifen consumption in patients with BC. Material and Methods This cross-sectional observational study was carried out from July to September 2023 in the medical oncology services of the “Virgen de la Puerta” - ESSALUD High Complexity Hospital and “Dr. Luis Pinillos Ganoza” - IREN Norte - Regional Institute of Neoplastic Diseases, in Trujillo - Peru. Overall, 200 adult patients diagnosed with BC were evaluated, of which 100 consumed tamoxifen and 100 did not. Inter- and intra-rater reliability was determined with respect to TL, resulting in intra-class correlation values RHO = 0.971 and interclass RHO = 0.938. The oncologist of the corresponding service performed BC diagnosis and stage. Poisson regression was used to analyze results with a significance level of p <0.05. Results No relationship was found between TL and tamoxifen consumption in patients with breast cancer ( p = 0.221); however, greater TL was observed in women who consumed tamoxifen for more than one year compared to those who did not use it ( p =0.025) and in older adult women compared to young women ( p =0.030). Conclusions There is a relationship between TL and time of use of tamoxifen in patients with BC, concluding that patients who consumed tamoxifen for more than one year had greater TL than those who did not. Furthermore, no relationship was found between TL and cancer stages, but there was greater TL in older adult patients and also in those who consumed tamoxifen and did not receive chemotherapy or radiotherapy. Key words: Tooth loss, tamoxifen, breast cancer, chemotherapy, radiotherapy.

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Dissimilar action of tamoxifen and 4-hydroxytamoxifen on phosphatidylcholine model membranes

Cited by 3 publications

References 52 publications

On the Mechanism of Membrane Permeabilization by Tamoxifen and 4-Hydroxytamoxifen

On the Mechanism of Membrane Permeabilization by Tamoxifen and 4-Hydroxytamoxifen

Influence of CYP2D6 and its polymorphic forms on the metabolism of tamoxifen in therapy of luminal forms of breast cancer

Tooth loss in breast cancer patients: A comparison between tamoxifen-treated and non-treated patients

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