• Journal of Menopausal Medicine
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• 제24권3호
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• pp.183-187
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• 2018

Objectives: The present mini review aimed to summarize the existing knowledge regarding the beneficial and adverse effects of raloxifene in menopausal women. Methods: This study is a review of relevant publications about the effects of raloxifene on sleep disorder, depression, venous thromboembolism, the plasma concentration of lipoprotein, breast cancer, and cognitive function among menopausal women. Results: Raloxifene showed no significant effect on depression and sleep disorder. Verbal memory improved with administration of 60 mg/day of raloxifene while a mild cognitive impairment risk reduction by 33% was observed with administration of 120 mg/day of raloxifene. Raloxifene was associated with a 50% decrease in the need for prolapse surgery. The result of a meta-analysis showed a significant decline in the plasma concentration of lipoprotein in the raloxifene group compared to placebo (standardized mean difference, -0.43; 10 trials). A network meta-analysis showed that raloxifene significantly decreased the risk of breast cancer (relative risk, 0.572; 95% confidence interval, 0.327-0.881; P = 0.01). In terms of adverse effects of raloxifene, the odds ratio (OR) was observed to be 1.54 (P = 0.006), indicating 54% increase in the risk of deep vein thrombosis (DVT) while the OR for pulmonary embolism (PE) was 1.05, suggesting a 91% increase in the risk of PE alone (P = 0.03). Conclusions: Raloxifene had no significant effect on depression and sleep disorder but decreased the concentration of lipoprotein. Raloxifene administration was associated with an increased risk of DVT and PE and a decreased risk of breast cancer and pelvic organ prolapse in postmenopausal women.

• Molecules and Cells
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• 제38권2호
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• pp.138-144
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• 2015

Raloxifene is a selective estrogen receptor modulator (SERM) that binds to the estrogen receptor (ER), and exhibits potent anti-tumor and autophagy-inducing effects in breast cancer cells. However, the mechanism of raloxifene-induced cell death and autophagy is not well-established. So, we analyzed mechanism underlying death and autophagy induced by raloxifene in MCF-7 breast cancer cells. Treatment with raloxifene significantly induced death in MCF-7 cells. Raloxifene accumulated GFP-LC3 puncta and increased the level of autophagic marker proteins, such as LC3-II, BECN1, and ATG12-ATG5 conjugates, indicating activated autophagy. Raloxifene also increased autophagic flux indicators, the cleavage of GFP from GFP-LC3 and only red fluorescence-positive puncta in mRFP-GFP-LC3-expressing cells. An autophagy inhibitor, 3-methyladenine (3-MA), suppressed the level of LC3-II and blocked the formation of GFP-LC3 puncta. Moreover, siRNA targeting BECN1 markedly reversed cell death and the level of LC3-II increased by raloxifene. Besides, raloxifene-induced cell death was not related to cleavage of caspases-7, -9, and PARP. These results indicate that raloxifene activates autophagy-dependent cell death but not apoptosis. Interestingly, raloxifene decreased the level of intracellular adenosine triphosphate (ATP) and activated the AMPK/ULK1 pathway. However it was not suppressed the AKT/mTOR pathway. Addition of ATP decreased the phosphorylation of AMPK as well as the accumulation of LC3-II, finally attenuating raloxifene-induced cell death. Our current study demonstrates that raloxifene induces autophagy via the activation of AMPK by sensing decreases in ATP, and that the overactivation of autophagy promotes cell death and thereby mediates the anti-cancer effects of raloxifene in breast cancer cells.

• Journal of Korean Biological Nursing Science
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• 제12권1호
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• pp.63-72
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• 2010

Purpose: The purpose of this study is to assess the effects of raloxifene in prevention of cardiovascular disease in postmenopausal women. Methods: A systematic literature review was conducted. Data sources: The existing literature from 1986 to 2009 was searched electronically using the data base of Medline with the key words of hypertension, obesity, diabetes, cholesterol, lipid, myocardial infarction, coronary events with combination of raloxifene. Study selection: The criteria for inclusion in the review were 1) an randomized clinical trial (RCT), 2) postmenopausal women, 3) English or Korean language. Finally, 15 articles were included in the review. Data extraction: Findings from the studies were organized according to the results of lipid profile changes by two authors. Results: Among 15 articles, 12 studies reported the beneficial effects of raloxifene on LDL cholesterol and 9 studies on total cholesterol in the postmenopausal women. Conclusion: The consistent results on reduction of LDL cholesterol and total cholesterol in raloxifene using postmenopausal women were confirmed. However, the effect of raloxifene on other components of lipid profile and endothelial function were still remaining controversial.

• Molecules and Cells
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• 제26권1호
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• pp.48-52
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• 2008

We here demonstrate an anti-inflammatory action of raloxifene, a selective estrogen receptor modulator, in lipopolysaccharide (LPS)-induced murine macrophage RAW264.7 cells. Treatment with raloxifene at micromolar concentrations suppressed the production of nitric oxide (NO) by down-regulating expression of the inducible nitric oxide synthase (iNOS) gene in LPS-activated cells. The decreased expression of iNOS and subsequent reduction of NO were due to inhibition of nuclear translocation of transcription factor NF-${\kappa}B$. These effects were significantly inhibited by exposure to the phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor, LY294002, or by expression of a dominant negative mutant of PI 3-kinase. In addition, pretreatment with raloxifene reduced LPS-induced Akt phosphorylation as well as NF-${\kappa}B$ DNA binding activity and NF-${\kappa}B$-dependent reporter gene activity. Thus our findings indicate that raloxifene exerts its anti-inflammatory action in LPS-stimulated macrophages by blocking the PI 3-kinase-Akt-NF-${\kappa}B$ signaling cascade, and eventually reduces expression of pro-inflammatory genes such as iNOS.

• BMB Reports
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• 제53권3호
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• pp.166-171
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• 2020

A chemical library comprising 2,354 drug-like compounds was screened using a transcription and replication-competent viruslike particle (trVLP) system implementing the whole Ebola virus (EBOV) life cycle. Dose-dependent inhibition of Ebola trVLP replication was induced by 15 hit compounds, which primarily target different types of G protein-coupled receptors (GPCRs). Based on the chemical structure, the compounds were divided into three groups, diphenylmethane derivatives, promazine derivatives and chemicals with no conserved skeletons. The third group included sertindole, raloxifene, and ibutamoren showing prominent antiviral effects in cells. They downregulated the expression of viral proteins, including the VP40 matrix protein and the envelope glycoprotein. They also reduced the amount of EBOV-derived tetracistronic minigenome RNA incorporated into progeny trVLPs in the culture supernatant. Particularly, ibutamoren, which is a known agonist of growth hormone secretagogue receptor (GHSR), showed the most promising antiviral activity with a 50% effective concentration of 0.2 μM, a 50% cytotoxic concentration of 42.4 μM, and a selectivity index of 222.8. Here, we suggest a strategy for development of anti-EBOV therapeutics by adopting GHSR agonists as hit compounds.

• 한국동물학회:학술대회논문집
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• 한국동물학회 2003년도 한국생물과학협회 학술발표대회
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• pp.166.2-166
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• 2003

No Abstract, See Full Text

• 한국임상약학회지
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• 제24권2호
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• pp.98-105
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• 2014

Purpose: The aim of this study was to compare retrospectively the efficacy of anti-osteoporotic agents (RAL-Raloxifene 60 mg, ALD-weekly alendronate 70 mg, RSD-weekly risedronate 35 mg, AVD3-weekly alendronate 70 mg/vitamin $D_3$ 2800IU, IBD-quarterly IV ibandronate 3 mg/3 ml, ZLD-yearly IV zoledronate 5 mg/100 ml) in postmenopausal patients with osteoporosis or osteopenia. Method: This study retrospectively reviewed medical record and compared the lumbar spine BMD percentage changes of each medicine group one year later from the baseline. 209 patients (27, 50, 60, 30, 35, and 7 patients in RAL, ALD, RSD, AVD3, IBD, and ZLD groups, respectively) are within the inclusion criteria for the study. Results: From baseline to month 12, lumbar spine BMD increased significantly larger with bisphosphonate groups, compared to SERM (p < 0.05). In all bisphosphonate groups, the lumbar spine BMD were increased significantly from baseline. Of the bisphosphonates, the changes from baseline in BMD of IV bisphosphonates were more larger than those of oral bisphosphonates, and yearly, quarterly bisphosphonates yielded significantly greater BMD gains, compared with weekly bisphosphonate groups (p<0.05). In addition, patients receiving 70 mg weekly alendronate+vitamin D3 had greater gains in BMD than alendronate Single preparation (p<0.05). Conclusion: Bisphosphonates yielded significantly greater BMD gains than SERM. Of the bisphosphonates, the changes from baseline in BMD of yearly, quarterly IV bisphosphonates yielded significantly greater BMD gains, compared with weekly oral bisphosphonate groups. In addition, vitamin D3 plays an significant role in BMD gains.

• Journal of Yeungnam Medical Science
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• 제16권2호
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• pp.155-168
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• 1999

Osteoporosis is one of the most important public health problems facing the aging population. Drug therapy for osteoporosis can be divided operationally into two main categories: drugs that inhibit bone resorption, and thus reduce bone turnover, and those that stimulate bone formation, exerting an anabolic effect. Antiresorptive agents such as estrogens, calcitonin, and bisphosphonates are most effective in the prevention of osteoporosis. Formation-stimulating agents such as sodium fluoride or monofluorophosphate, parathyroid hormone fragments, and anabolic steroids are of potential value in the treatment of established osteoporosis, where bone mass is already low and benefit from antiresorptive drugs is likely to be small Recently, raloxifene, a selective estrogen receptor modulator, has become available in various countries for clinical use in the treatment of involutional osteoporsis. This paper will review the use of these drugs in postmenopausal woman.

• Journal of Yeungnam Medical Science
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• 제25권1호
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• pp.19-30
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• 2008

골다공증은 골밀도와 골의 질로 구성되는 골의 강도가 손상됨으로 골절의 위험이 높아지는 골격질환이며, 최근 유병율이 점차 증가하고 있는 추세이다. 임상적으로 무증상인 경우가 많으며 방사선학적 검사인 단순 방사선 검사, 골 스캔, CT, MRI 등이 골밀도 및 골절의 진단에 유용하다. 골밀도의 정량적 검사로는 이중에너지 방사선 흡수법, 정량적 전산화 단층촬영이 사용되고 있다. 골다공증의 진단은 WHO 기준에 따라 T-score가 -2.5 이하일 경우 진단할 수 있다. 그 외에 생화학적 골표지자들도 진단에 도움이 된다. 골다공증 치료제는 골흡수억제제와 골형성자극제(formation stimulator)로 나눌 수 있는데 골흡수억제제로는 칼슘, 에스트로겐, 칼시토닌, 비스포스포네이트(bisphosphonate), 비타민 D 등이 있으며 골량을 증가시키는 골형성자극제로는 현재 부갑상선 호르몬이 유일하며 최근 strontium ranelate가 추가되었다. 일일 1200 mg의 칼슘과 800 IU 의 비타민 D 섭취가 권장되고 있으며, 폐경기 여성에서 에스트로겐이 효과가 입증되었고 골다공증으로 인한 통증에는 칼시토닌이 효과가 있다. 비스포스포네이트는 폐경 후 골다공증의 치료, 예방 및 스테로이드에 의한 골다공증 치료에 대해 FDA의 승인을 받았다. 폐경 후 골다공증의 치료, 예방에 사용되는 SERM은 골의 질을 향상시킴으로써 골절을 예방한다고 알려져 있다. 골형성자극제인 부갑상선 호르몬이 골절의 위험을 감소시킨다고 보고된 바 있으며, strontium은 최근에 개발된 약제로 3상 연구에서 골절 위험율 감소효과를 보였으나 더 많은 연구가 필요할 것으로 생각된다.

• Biomolecules & Therapeutics
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• 제30권4호
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• pp.309-319
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• 2022

Metabolic bone diseases are serious health issues worldwide, since several million individuals over the age of 50 are at risk of bone damage and should be worried about their bone health. One in every two women and one in every four men will break a bone during their lifetime due to a metabolic bone disease. Early detection, raising bone health awareness, and maintaining a balanced healthy diet may reduce the risk of skeletal fractures caused by metabolic bone diseases. This review compiles information on the most common metabolic bone diseases (osteoporosis, primary hyperparathyroidism, osteomalacia, and fluorosis disease) seen in the global population, including their symptoms, mechanisms, and causes, as well as discussing their prevention and the development of new drugs for treatment. A large amount of research literature suggests that balanced nutrition and balanced periodic supplementation of calcium, phosphate, and vitamin D can improve re-absorption and the regrowth of bones, and inhibit the formation of skeletal fractures, except in the case of hereditary bone diseases. Meanwhile, new and improved drug formulations, such as raloxifene, teriparatide, sclerostin, denosumab, and abaloparatide, have been successfully developed and administered as treatments for metabolic bone diseases, while others (romososumab and odanacatib) are in various stages of clinical trials.