Dataset Information

The Silkworm Carboxypeptidase Inhibitor Prevents Gastric Cancer Cells' Proliferation through the EGF/EGFR Signaling Pathway.

ABSTRACT: Gastric cancer is a common malignant tumor originating from the gastric mucosa epithelium. Studies have shown that bioactive substances such as antimicrobial peptides and cantharidin contained in a variety of insects can exert anti-cancer functions; when compared with chemotherapy drugs, these bioactive substances have less toxicity and reduced side effects. Here, we report the first Bombyx mori carboxypeptidase inhibitor that is specifically and highly expressed in silk glands, which can significantly prevent the proliferation of gastric cancer cells by inhibiting the MAPK/ERK pathway initiated by EGF/EGFR through the promotion of expression of the proto-oncogene c-Myc, thereby affecting the expression of related cyclins. Through molecular docking and virtual screening of silkworm carboxypeptidase inhibitors and epidermal growth factor receptors, we identified a polypeptide that overlapped with existing small-molecule inhibitors of the receptor. In the present work, we explore the medicinal potential and application of silkworm carboxypeptidase inhibitors to promote the development of anti-tumor drugs from insect-derived substances.

SUBMITTER: Ye J

PROVIDER: S-EPMC9861121 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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The Silkworm Carboxypeptidase Inhibitor Prevents Gastric Cancer Cells' Proliferation through the EGF/EGFR Signaling Pathway.

Ye Junhong J Li Jifu J Zhao Ping P

International journal of molecular sciences 20230105 2

Gastric cancer is a common malignant tumor originating from the gastric mucosa epithelium. Studies have shown that bioactive substances such as antimicrobial peptides and cantharidin contained in a variety of insects can exert anti-cancer functions; when compared with chemotherapy drugs, these bioactive substances have less toxicity and reduced side effects. Here, we report the first <i>Bombyx mori</i> carboxypeptidase inhibitor that is specifically and highly expressed in silk glands, which can ...[more]

PMID: 36674593

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Project description:Inappropriate activation of the renin-angiotensin-aldosterone system (RAAS) is an important factor in the development of hypertension. Excessive aldosterone can lead to myocardial extracellular matrix collagen proliferation, fibrosis, and cardiomyocyte hypertrophy and aggravate maladaptive remodeling. The results of our previous clinical and animal experiments suggested that Zi Shen Huo Luo Formula (ZSHLF) combined with perindopril can effectively control the process of left ventricular hypertrophy (LVH). The purpose of this study was to investigate whether ZSHLF-treated serum inhibits the membrane localization of the striatin-mediated mineralocorticoid receptor (MR) and affects MR-mediated nongenomic effects and the downstream epidermal growth factor receptor (EGFR)/extracellular regulated kinase (ERK) signaling pathways, thereby improving aldosterone-induced myocardial remodeling. Serum containing ZSHLF was prepared and used to treat rat cardiomyocytes and cardiac fibroblasts in vitro after aldosterone induction and striatin knockdown by small interfering RNA (siRNA). Cell-based assays were carried out to determine the cardiomyocyte surface area and assess the proliferation rate and hydroxyproline secretion of cardiac fibroblasts. Quantitative real-time PCR (qRT-PCR), immunoprecipitation (IP), and Western blotting were performed to evaluate the striatin-mediated MR/EGFR/ERK signaling pathway. In the present study, ZSHLF attenuated the aldosterone-induced hypertrophy of cardiomyocytes and inhibited the proliferation and collagen synthesis of cardiac fibroblasts. ZSHLF also reduced striatin mRNA expression and inhibited striatin and MR binding, membrane MR protein expression, and EGFR and ERK1/2 phosphorylation. Furthermore, after striatin silencing with siRNA, some of the effects of ZSHLF were not changed significantly. In conclusion, ZSHLF inhibits the downstream EGFR/ERK signaling pathway by blocking the striatin-mediated membrane localization of MR, which may be an important molecular mechanism by which ZSHLF improves aldosterone-induced myocardial remodeling.

Dataset Information

The Silkworm Carboxypeptidase Inhibitor Prevents Gastric Cancer Cells' Proliferation through the EGF/EGFR Signaling Pathway.

Publications

The Silkworm Carboxypeptidase Inhibitor Prevents Gastric Cancer Cells' Proliferation through the EGF/EGFR Signaling Pathway.

Similar Datasets

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