Anordrin Eliminates Tamoxifen Side Effects without Changing Its Antitumor Activity

Gu, Wenwen; Xu, Wenping; Sun, Xiaoxi; Zeng, Bu‐Bing; Wang, Shuangjie; Dong, Nian; Zhang, Xu; Chen, Chengshui; Yang, Long; Chen, Guowu; Xin, Aijie; Ni, Zhong; Wang, Jian; Yang, Jun

doi:10.1038/srep43940

Cited by 12 publications

(8 citation statements)

References 22 publications

(59 reference statements)

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“…More recently, a similar strategy has been investigated by targeting plasma membrane ERs. More specifically, Gu et al showed that the ER36 antagonist anordrin prevents tamoxifen-induced DISH in mice [ 46 ]. Importantly, anordrin also suppresses the growth of breast and endometrial cancer cells in vitro, suggesting that its combination with tamoxifen should not impair the antineoplastic effect of this drug on breast cancer and should also help reduce the risk of tamoxifen-induced endometrial cancer.…”

Section: Tamoxifen Corticosteroids and Anabolic Agents: If Multiple Intracellular Receptors Are Involved Just Modulate The Right One To Rmentioning

confidence: 99%

New Avenues for Treatment and Prevention of Drug-Induced Steatosis and Steatohepatitis: Much More Than Antioxidants

et al. 2021

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Drug-induced lipid accumulation in the liver may induce two clinically relevant conditions, drug-induced steatosis (DIS) and drug-induced steatohepatitis (DISH). The list of drugs that may cause DIS or DISH is long and heterogeneous and includes therapeutically relevant molecules that cannot be easily replaced by less hepatotoxic medicines, therefore making specific strategies necessary for DIS/DISH prevention or treatment. For years, the only available tools to achieve these goals have been antioxidant drugs and free radical scavengers, which counteract drug-induced mitochondrial dysfunction but, unfortunately, have only limited efficacy. In the present review we illustrate how in vitro preclinical research unraveled new key players in the pathogenesis of specific forms of DISH, and how, in a few cases, proof of

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Section: Tamoxifen Corticosteroids and Anabolic Agents: If Multiple Intracellular Receptors Are Involved Just Modulate The Right One To Rmentioning

confidence: 99%

New Avenues for Treatment and Prevention of Drug-Induced Steatosis and Steatohepatitis: Much More Than Antioxidants

et al. 2021

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“…It could play an important role in chemoprevention of breast cancer in women with high risk factors, but this still remains controversial [6]. Although the benefit of tamoxifen in the management of ER+ breast cancer has been established (low risk of recurrence and contralateral breast cancer), its risk of inducing endometrial cancer has also been recognized [7], thus raising the issue of how to counteract the tamoxifen-induced endometrial hyperplasia. Numerous authors have demonstrated that the chemopreventive effects of tamoxifen could be improved by combining it with substances that could potentiate its antitumor activity or mitigate its side effects on the endometrium [5,8].…”

Section: Introductionmentioning

confidence: 99%

Ethanol-Extracted Cameroonian Propolis Counteracts Tamoxifen-Induced Endometrial Hyperplasia by Modulating Apoptosis and Proliferation-Regulating Proteins in the Ovaries of Intact Wistar Rats

Awounfack

Zingue

Koumabas

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Tamoxifen is the most common adjuvant that has been widely used in the treatment of positive estrogen receptor (ER+) breast cancer for over 20 years. However, long term exposure to tamoxifen doubles the risk of endometrial cancer. The association of tamoxifen with antiproliferative substances could abrogate its side effects on the endometrium. Recently, we demonstrated that ethanol-extracted Cameroonian propolis (EECP) has chemopreventive effects on ER+ breast cancer in rats. This study evaluated the capability of EECP to counteract tamoxifen-induced endometrial hyperplasia, without altering its effect on the breast. Thirty-six rats of ∼2 months were coadministered either EECP (16.5, 50, and 150 mg/kg BW) or fulvestrant (300 μg/kg BW) and tamoxifen (10 mg/kg BW) for 8 weeks. Afterward, the relative weights and histomorphometry of the uterus, vagina, ovaries, and mammary gland were assessed. The expression of some proteins of proliferation (PCNA), angiogenesis (VEGF), and apoptosis (Bax, Bcl-2, and caspase-3) was measured by immunohistochemistry. Rats that received only tamoxifen had endometrial hyperplasia compared to normal rats. EECP and fulvestrant protected the rats against tamoxifen-induced endometrial hyperplasia. A significant decrease in uterine wet weight ( p < 0.01 ); endometrial height ( p < 0.001 ); and expression of PCNA, Bcl-2, and VEGF proteins as well as a significant increase in the expression of Bax and caspase-3 proteins was observed in the EECP group compared to the Tamox group. EECP did not change the effects of tamoxifen on the breast. In summary, Cameroonian propolis which is efficacious in preventing breast cancer can also be a good complementary medicine to prevent tamoxifen-induced endometrial cancer in tamoxifen users.

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“…Tamoxifen (TAM) is used for the treatment of breast cancer widely 3 . It is noticeable, however, that hepatocyte steatosis has been described in studies of patients with breast cancer because of TAM, 4,5 and TAM is known to induce this condition in half of the patients within the first 2 years of TAM treatment 6‐8 . Therapeutic intervention to prevent TAM‐induced hepatocyte steatosis may improve the safety of TAM usage 9 .…”

Section: Introductionmentioning

confidence: 99%

Tamoxifen induces fatty liver disease in breast cancer through the MAPK8/FoxO pathway

Gong

Tang

Luo

et al. 2020

Clinical & Translational Med

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Background Prevention of metabolic complications of long‐term adjuvant endocrine therapy in breast cancers remained a challenge. We aimed to investigate the molecular mechanism in the development of tamoxifen (TAM)‐induced fatty liver in both estrogen receptor (ER)‐positive and ER‐negative breast cancer. Methods and results First, the direct protein targets (DPTs) of TAM were identified using DrugBank5.1.7. We found that mitogen‐activated protein kinase 8 (MAPK8) was one DPT of TAM. We identified significant genes in breast cancer and fatty liver disease (FLD) using the MalaCards human disease database. Next, we analyzed the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of those significant genes in breast cancer and FLD using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). We found that overlapping KEGG pathways in these two diseases were MAPK signaling pathway, Forkhead box O (FoxO) signaling pathway, HIF‐1 signaling pathway, AGE‐RAGE signaling pathway in diabetic complications, and PI3K‐Akt signaling pathway. Furthermore, the KEGG Mapper showed that the MAPK signaling pathway was related to the FoxO signaling pathway. Finally, the functional relevance of breast cancer and TAM‐induced FLD was validated by Western blot analysis. We verified that TAM may induce fatty liver in breast cancer through the MAPK8/FoxO signaling pathway. Conclusion Bioinformatics analysis combined with conventional experiments may improve our understanding of the molecular mechanisms underlying side effects of cancer drugs, thereby making this method a new paradigm for guiding future studies on this issue.

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Anordrin Eliminates Tamoxifen Side Effects without Changing Its Antitumor Activity

Cited by 12 publications

References 22 publications

New Avenues for Treatment and Prevention of Drug-Induced Steatosis and Steatohepatitis: Much More Than Antioxidants

New Avenues for Treatment and Prevention of Drug-Induced Steatosis and Steatohepatitis: Much More Than Antioxidants

Ethanol-Extracted Cameroonian Propolis Counteracts Tamoxifen-Induced Endometrial Hyperplasia by Modulating Apoptosis and Proliferation-Regulating Proteins in the Ovaries of Intact Wistar Rats

Tamoxifen induces fatty liver disease in breast cancer through the MAPK8/FoxO pathway

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