Securinine inhibits the tumor growth of human bladder cancer cells by suppressing Wnt/ β-catenin signaling pathway and activating p38 and JNK signaling pathways
In this study, we evaluated the potential anti-tumor effect of securinine (SEC), a natural alkaloid from Securinega suffruticosa, on BC cells in vitro and in vivo, and delineated the underlying mechanism. We found that SEC inhibited the proliferation, migration and invasion, induced the apoptosis of BC cells in vitro, and retarded the xenograft tumor growth of BC cell in vivo. Notably, SEC had a promising safety profile because it presented no or low toxicity on normal cells and mice. Mechanistically, SEC inactivated Wnt/β-catenin signaling pathway while activated p38 and JNK signaling pathway. Moreover, β-catenin overex...
Source: Biochemical Pharmacology - March 14, 2024 Category: Drugs & Pharmacology Authors: Liping Xie Shiqiong Liang Habu Jiwa Lulu Zhang Qiuping Lu Xiaoxuan Wang Lijuan Luo Haichao Xia Ziyun Li Jiayu Wang Xiaoji Luo Jinyong Luo Source Type: research

Emerging models for studying adipose tissue metabolism
In conclusion, a diverse array of research models is crucial for deciphering adipose metabolism. By leveraging traditional adipocyte cell cultures, primary-derived cells, spheroids, AOoCs, and lower organism models, we bridge the gap between animal testing and a more ethical, scientifically robust, and human-relevant approach, advancing our understanding of adipose tissue metabolism and its impact on health.PMID:38484851 | DOI:10.1016/j.bcp.2024.116123 (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - March 14, 2024 Category: Drugs & Pharmacology Authors: Ignasi Mora Francesc Puiggr òs Florenci Serras Katherine Gil-Cardoso Xavier Escot é Source Type: research

Phytic acid promotes high glucose-mediated bone marrow mesenchymal stem cells osteogenesis via modulating circEIF4B that sponges miR-186-5p and complexes with IGF2BP3
In this study, in virto experiments demonstrated that PA treatment effectively improved the osteogenic capability of high glucose-mediated BMSCs. Differentially expressed circRNAs in PA-induced BMSCs were identified using circRNA microarray analysis. Here, our findings highlight an upregulation of circEIF4B expression in BMSCs stimulated with PA under a high-glucose microenvironment. Further investigations demonstrated that circEIF4B overexpression promoted high glucose-mediated BMSC osteogenesis. In contrast, circEIF4B knockdown exerted the opposite effect. Mechanistically, circEIF4B sequestered microRNA miR-186-5p and tr...
Source: Biochemical Pharmacology - March 11, 2024 Category: Drugs & Pharmacology Authors: Jin Wu Xiang Li Hepeng Nie Yue Shen Zixiang Guo Catherine Huihan Chu Kunzhan Cai Chunbo Tang Source Type: research

Unraveling lipid metabolism reprogramming for overcoming drug resistance in melanoma
Biochem Pharmacol. 2024 Mar 10;223:116122. doi: 10.1016/j.bcp.2024.116122. Online ahead of print.ABSTRACTCutaneous melanoma is the deadliest form of skin cancer, and its incidence is continuing to increase worldwide in the last decades. Traditional therapies for melanoma can easily cause drug resistance, thus the treatment of melanoma remains a challenge. Various studies have focused on reversing the drug resistance. As tumors grow and progress, cancer cells face a constantly changing microenvironment made up of different nutrients, metabolites, and cell types. Multiple studies have shown that metabolic reprogramming of ca...
Source: Biochemical Pharmacology - March 11, 2024 Category: Drugs & Pharmacology Authors: Ruilong Wang Qin Yan Xiao Liu Jinfeng Wu Source Type: research

Phytic acid promotes high glucose-mediated bone marrow mesenchymal stem cells osteogenesis via modulating circEIF4B that sponges miR-186-5p and complexes with IGF2BP3
In this study, in virto experiments demonstrated that PA treatment effectively improved the osteogenic capability of high glucose-mediated BMSCs. Differentially expressed circRNAs in PA-induced BMSCs were identified using circRNA microarray analysis. Here, our findings highlight an upregulation of circEIF4B expression in BMSCs stimulated with PA under a high-glucose microenvironment. Further investigations demonstrated that circEIF4B overexpression promoted high glucose-mediated BMSC osteogenesis. In contrast, circEIF4B knockdown exerted the opposite effect. Mechanistically, circEIF4B sequestered microRNA miR-186-5p and tr...
Source: Biochemical Pharmacology - March 11, 2024 Category: Drugs & Pharmacology Authors: Jin Wu Xiang Li Hepeng Nie Yue Shen Zixiang Guo Catherine Huihan Chu Kunzhan Cai Chunbo Tang Source Type: research

Unraveling lipid metabolism reprogramming for overcoming drug resistance in melanoma
Biochem Pharmacol. 2024 Mar 9:116122. doi: 10.1016/j.bcp.2024.116122. Online ahead of print.ABSTRACTCutaneous melanoma is the deadliest form of skin cancer, and its incidence is continuing to increase worldwide in the last decades. Traditional therapies for melanoma can easily cause drug resistance, thus the treatment of melanoma remains a challenge. Various studies have focused on reversing the drug resistance. As tumors grow and progress, cancer cells face a constantly changing microenvironment made up of different nutrients, metabolites, and cell types. Multiple studies have shown that metabolic reprogramming of cancer ...
Source: Biochemical Pharmacology - March 11, 2024 Category: Drugs & Pharmacology Authors: Ruilong Wang Qin Yan Xiao Liu Jinfeng Wu Source Type: research

Phytic acid promotes high glucose-mediated bone marrow mesenchymal stem cells osteogenesis via modulating circEIF4B that sponges miR-186-5p and complexes with IGF2BP3
In this study, in virto experiments demonstrated that PA treatment effectively improved the osteogenic capability of high glucose-mediated BMSCs. Differentially expressed circRNAs in PA-induced BMSCs were identified using circRNA microarray analysis. Here, our findings highlight an upregulation of circEIF4B expression in BMSCs stimulated with PA under a high-glucose microenvironment. Further investigations demonstrated that circEIF4B overexpression promoted high glucose-mediated BMSC osteogenesis. In contrast, circEIF4B knockdown exerted the opposite effect. Mechanistically, circEIF4B sequestered microRNA miR-186-5p and tr...
Source: Biochemical Pharmacology - March 11, 2024 Category: Drugs & Pharmacology Authors: Jin Wu Xiang Li Hepeng Nie Yue Shen Zixiang Guo Catherine Huihan Chu Kunzhan Cai Chunbo Tang Source Type: research

Unraveling lipid metabolism reprogramming for overcoming drug resistance in melanoma
Biochem Pharmacol. 2024 Mar 9:116122. doi: 10.1016/j.bcp.2024.116122. Online ahead of print.ABSTRACTCutaneous melanoma is the deadliest form of skin cancer, and its incidence is continuing to increase worldwide in the last decades. Traditional therapies for melanoma can easily cause drug resistance, thus the treatment of melanoma remains a challenge. Various studies have focused on reversing the drug resistance. As tumors grow and progress, cancer cells face a constantly changing microenvironment made up of different nutrients, metabolites, and cell types. Multiple studies have shown that metabolic reprogramming of cancer ...
Source: Biochemical Pharmacology - March 11, 2024 Category: Drugs & Pharmacology Authors: Ruilong Wang Qin Yan Xiao Liu Jinfeng Wu Source Type: research

Unraveling the immune landscape and therapeutic biomarker PMEPA1 for oxaliplatin resistance in colorectal cancer: A comprehensive approach
This study aims to comprehensively investigate the immune landscape, targeted therapeutic biomarkers, and mechanisms that influence OXA resistance in CRC. Our results demonstrated that our OXA resistance-based CRC prognostic model not only provides risk assessment for patients but also reflects the immune landscape of patients. Additionally, we identified prostate transmembrane protein, androgen-induced 1 (PMEPA1) as a promising molecular targeted therapeutic biomarker for patients with OXA-resistant CRC. The mechanism of PMEPA1 may involve cell adhesion, pathways in cancer, and the TGF-β signaling pathway. Furthermore, a...
Source: Biochemical Pharmacology - March 10, 2024 Category: Drugs & Pharmacology Authors: Zhengguang Zhang Tianming Lu Zhe Zhang Zixian Liu Ruoning Qian Ruogu Qi Fuqiong Zhou Min Li Source Type: research

The role of G protein-coupled receptor kinases in GLP-1R β-arrestin recruitment and internalisation
This study advances mechanistic understanding of agonist-mediated GLP-1R internalisation and provides novel insights into how GRKs may fine-tune GLP-1R signalling.PMID:38461904 | DOI:10.1016/j.bcp.2024.116119 (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - March 10, 2024 Category: Drugs & Pharmacology Authors: Samantha M McNeill Jessica Lu Carlo Marion C Carino Asuka Inoue Peishen Zhao Patrick M Sexton Denise Wootten Source Type: research

H3K18 lactylation-mediated VCAM1 expression promotes gastric cancer progression and metastasis via AKT-mTOR-CXCL1 axis
Biochem Pharmacol. 2024 Mar 8:116120. doi: 10.1016/j.bcp.2024.116120. Online ahead of print.ABSTRACTThe role of the Immunoglobulin Superfamily (IgSF) as adhesion molecules in orchestrating inflammation is pivotal, yet its specific involvement in gastric cancer (GC) remains unknown. We analyzed IgSF components and discerned conspicuously elevated VCAM1 expression in GC, correlating with a poor prognosis. Remarkably, VCAM1 enhances GC cell proliferation and migration by activating AKT-mTOR signaling. Moreover, lactate in the tumor microenvironment (TME) promotes dynamic lactylation of H3K18 (H3K18la), leading to transcriptio...
Source: Biochemical Pharmacology - March 10, 2024 Category: Drugs & Pharmacology Authors: Yupeng Zhao Jiang Jiang Peng Zhou Kaiyuan Deng Ziyuan Lui Mengqi Yang Xiao Yang Jianfang Li Ranran Li Jiazeng Xia Source Type: research

Sevelamer reverses liver fibrosis by deactivation of hepatic stellate cells
In this study, we investigated the antifibrotic effects of sevelamer-induced low inorganic phosphate (Pi) stress in vitro and in vivo and analyzed the detailed mechanisms. We found that low Pi stress could inhibit the proliferation of activated hepatic stellate cells (HSCs) by promoting apoptosis, effectively suppressing the migration and epithelial-mesenchymal transition (EMT) of hepatic stellate cells. Additionally, low Pi stress significantly increased the antioxidant stress response. It is worth noting that low Pi stress indirectly inhibited the activation and migration of HSCs by suppressing transforming growth factor...
Source: Biochemical Pharmacology - March 10, 2024 Category: Drugs & Pharmacology Authors: Yang-Feng Lv Chuan-Sheng Xie Zhi-Xing Liu Mei-Diao Kang Yue Liu Zi-Qiang Liao Yu-Long Ji Rui Zhao Yan-Shu Li Xiao-Yong Wei Rong-Guang Luo Qun Tang Source Type: research

Daurisoline suppress glioma progression by inhibiting autophagy through PI3K/AKT/mTOR pathway and increases TMZ sensitivity
Biochem Pharmacol. 2024 Mar 7:116113. doi: 10.1016/j.bcp.2024.116113. Online ahead of print.ABSTRACTGlioma is one of the most common primary malignant tumors of the central nervous system. Temozolomide (TMZ) is the only effective chemotherapeutic agent, but it easily develops resistance and has unsatisfactory efficacy. Consequently, there is an urgent need to develop safe and effective compounds for glioma treatment. The cytotoxicity of 30 candidate compounds to glioma cells was detected by the CCK-8 assay. Daurisoline (DAS) was selected for further investigation due to its potent anti-glioma effects. Our study revealed th...
Source: Biochemical Pharmacology - March 9, 2024 Category: Drugs & Pharmacology Authors: Hai-Tang Yin None Hui-Lu Ji-Hong Yang Qin Li Ming Li Qing-Qing Zhao Zhi-Peng Wen Source Type: research

Corynoxine triggers cell death via activating PP2A and regulating AKT-mTOR/GSK3 β axes in NSCLC
This study investigates the anticancer activity and pharmacological mechanisms of Corynoxine (Cory) in non-small cell lung cancer (NSCLC). Cory, a natural product derived from the Chinese herbal medicine Uncaria rhynchophylla, demonstrates promising pharmacological activity. Cell proliferation and viability were evaluated via MTT and colony formation assays. Flow cytometry was employed to analyze cell apoptosis, cycle distribution, and mitochondrial membrane potential. Autophagy was detected using fluorescence microscopy and electron microscopy. Western blotting, protein overexpression, gene knockdown, co-immunoprecipitati...
Source: Biochemical Pharmacology - March 9, 2024 Category: Drugs & Pharmacology Authors: Guoqing Hou Weihua Hu Yazhou Sang Xiaocai Gan Hui Xu Qiongying Hu Xuan Cao Source Type: research

The pathophysiology of visceral adipose tissues in cardiometabolic diseases
Biochem Pharmacol. 2024 Mar 7:116116. doi: 10.1016/j.bcp.2024.116116. Online ahead of print.ABSTRACTCentral pattern of fat distribution, especially fat accumulation within the intraabdominal cavity increases risks for cardiometabolic diseases. Portal hypothesis combined with a pathological remodeling in visceral fat is considered the major etiological factor explaining the independent contribution of visceral obesity to cardiometabolic diseases. Excessive remodeling in visceral fat during development of obesity leads to dysfunctions in the depot, characterized by hypertrophy and death of adipocytes, hypoxia, inflammation, ...
Source: Biochemical Pharmacology - March 9, 2024 Category: Drugs & Pharmacology Authors: Mi-Jeong Lee Jeehoon Kim Source Type: research