Discovering alkylamide derivatives of bexarotene as new therapeutic agents against triple-negative breast cancer

Chen, Luxi; Long, Chao; Nguyen, Jennifer; Kumar, Dhiraj; Lee, Jiyong

doi:10.1016/j.bmcl.2017.12.033

Cited by 8 publications

(5 citation statements)

References 27 publications

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“…Cytarabine, sorafenib and vorinostat presented higher sensitivity in high-risk group, which may lead to new treatment options for patients with early-stage CRC. In particular, bexarotene, bicalutamide and imatinib were also reported to suppress EMT and metastasis [25][26][27][28][29].…”

Section: Correlation Between the Tumor Immune Microenvironment And Th...mentioning

confidence: 99%

Identification of a Novel Amino Acid Metabolism-Related Gene Risk Signature as a Prognostic and Immunotherapeutic Efficiency Predictor for Colorectal Cancer

Zhu

Liu

Wang

et al. 2023

Preprint

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Background: The importance of amino acid metabolism in multiple cancers was investigated by accumulating researches. But the role of amino acid metabolism-related genes (AAMRGs) played in the colorectal cancer (CRC) progression remains unclear. Methods: The clinical information and RNA sequencing of CRC were acquired from The Cancer Genome Atlas (TCGA) databases and the Gene Expression Omnibus (GEO) databases, and amino acid metabolic gene data were downloaded from a published article in the journal Cell Reports. The Cox-LASSO analysis was adopted to establish a AAMRG prognostic signature. Kaplan–Meier (K-M) survival curve and receiver operating characteristic (ROC) curve were adopted to estimate the prognostic capacity of our risk signature. RT‒qPCR was adopted to estimate the expression of AAMRGs in clinical samples. Moreover, gene set enrichment analysis (GSEA) was adopted and according to result of GSEA, further investigation was conducted in immune infiltration, somatic mutation, drug sensitivity and EMT. Result: The activity of amino acid metabolism was significantly increased in CRC. A 10-AAMRG prognostic signature was established and the CRC samples were classified into two groups (high-risk and low-risk). Risk score was analyzed to be an independent factor of CRC to affect cancer progression. The result of RT-qPCR showed that among 10 AAMRGs, the expression abundances of MRPS23 and TRAP1 in CRC tissues and adjacent normal colorectal tissues were both upregulated. According to GSEA outcomes and further analyses, significant differences were observed in immune infiltration and EMT between two risk groups. Furthermore, analysis of drug sensitivity illustrated that some chemotherapy drugs had higher IC50 values in low-risk group, including bexarotene, bicalutamide and imatinib. Conclusion: The 10-AAMRG signature we built is a prospective biomarker, which has great potentiality to predict CRC therapeutic responses and clinical prognosis.

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Section: Correlation Between the Tumor Immune Microenvironment And Th...mentioning

confidence: 99%

Identification of a Novel Amino Acid Metabolism-Related Gene Risk Signature as a Prognostic and Immunotherapeutic Efficiency Predictor for Colorectal Cancer

Zhu

Liu

Wang

et al. 2023

Preprint

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“…Alkamides have also been investigated as treatments for cancer. For example, alkamide derivatives of bexarotene were able to induce apoptosis and prevent cell migration and proliferation in triple-negative breast cancer cells, while showing no cytotoxic effects against normal mammary epithelial cells [69]. In addition, a panel of alkamides with varying structure and molecular weights were able to induce differentiation of human leukemia cells to granulocyte-like cells [70].…”

Section: Cancer Cellsmentioning

confidence: 99%

The Structure and Function of Alkamides in Mammalian Systems

Johnstone¹,

Laster²

2022

Natural Drugs From Plants

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Alkamides, or alkylamides, are fatty acid amides produced by plants from the genera Echinacea, Acmella, Spilanthes, and Heliopsis among others. Alkamides contain varying head groups, an amide moiety, and a fatty acid tail with varying numbers of carbons and double and triple bonds. Extracts from these plants have been used worldwide by native peoples for the treatment of numerous medical disorders, including bacterial and viral infections, inflammation, liver and kidney disorders, and pain. In vitro, these molecules display a variety of different activities depending on the cell type tested. Studies with neurons, macrophages and mast cells have revealed interactions between alkamides and a number of different cells surface receptors and intracellular signaling molecules. Generally, the alkamides have been found to exert suppressive effects, inhibiting cellular activation. In this report we introduce the structure of alkamides and review their effects in a number of different cellular systems. We also describe structure:function studies that have been performed with alkamides. While these studies have not as yet revealed general rules for alkamide activity, interesting insights have been revealed. The stage is set for the development of synthetic, designer alkamides with targeted in vivo activities.

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“…In addition, it inhibited NOTCH signaling pathway which is related to cell invasion and migration [146]. Furthermore, several apocarotenoids inhibited migration and EMT associated factors in BT-549 and MDA-MB-231 [147]. Therefore, carotenoids and apocarotenoids could be helpful preventing metastasis in triple negative tumors.…”

Section: In Vitro and In Vivo Studiesmentioning

confidence: 99%

Halophilic Carotenoids and Breast Cancer: From Salt Marshes to Biomedicine

Giani

Montoyo-Pujol²,

Peiró³

et al. 2021

Marine Drugs

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Breast cancer is the leading cause of death among women worldwide. Over the years, oxidative stress has been linked to the onset and progression of cancer. In addition to the classical histological classification, breast carcinomas are classified into phenotypes according to hormone receptors (estrogen receptor—RE—/progesterone receptor—PR) and growth factor receptor (human epidermal growth factor receptor—HER2) expression. Luminal tumors (ER/PR-positive/HER2-negative) are present in older patients with a better outcome. However, patients with HER2-positive or triple-negative breast cancer (TNBC) (ER/PR/HER2-negative) subtypes still represent highly aggressive behavior, metastasis, poor prognosis, and drug resistance. Therefore, new alternative therapies have become an urgent clinical need. In recent years, anticancer agents based on natural products have been receiving huge interest. In particular, carotenoids are natural compounds present in fruits and vegetables, but algae, bacteria, and archaea also produce them. The antioxidant properties of carotenoids have been studied during the last years due to their potential in preventing and treating multiple diseases, including cancer. Although the effect of carotenoids on breast cancer during in vitro and in vivo studies is promising, clinical trials are still inconclusive. The haloarchaeal carotenoid bacterioruberin holds great promise to the future of biomedicine due to its particular structure, and antioxidant activity. However, much work remains to be performed to draw firm conclusions. This review summarizes the current knowledge on pre-clinical and clinical analysis on the use of carotenoids as chemopreventive and chemotherapeutic agents in breast cancer, highlighting the most recent results regarding the use of bacterioruberin from haloarchaea.

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Discovering alkylamide derivatives of bexarotene as new therapeutic agents against triple-negative breast cancer

Cited by 8 publications

References 27 publications

Identification of a Novel Amino Acid Metabolism-Related Gene Risk Signature as a Prognostic and Immunotherapeutic Efficiency Predictor for Colorectal Cancer

Identification of a Novel Amino Acid Metabolism-Related Gene Risk Signature as a Prognostic and Immunotherapeutic Efficiency Predictor for Colorectal Cancer

The Structure and Function of Alkamides in Mammalian Systems

Halophilic Carotenoids and Breast Cancer: From Salt Marshes to Biomedicine

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