August 11, 2024 longcha9

Study on the Induction of Apoptosis in SGC-7901 Cells by Extracellular Polysaccharides from Fusarium graminearum and Its Mechanism
Gastric cancer is the fifth most common cancer and the third leading cause of cancer death worldwide. Chemotherapy is commonly used in advanced stages, with common chemotherapy drugs such as cisplatin and 5-fluorouracil. However, the resistance and toxicity of chemotherapy drugs result in lower survival rates for patients. Polysaccharides, as natural high molecular weight polymers and their derivatives, have complex spatial structures and diverse biological activities. Many studies have shown that polysaccharides have good effects in preventing tumor occurrence and inhibiting tumor growth. They can alter cell membrane fluidity, inhibit tumor invasion and metastasis, and induce cell apoptosis and cycle arrest by regulating various signaling pathways and oncogene expression in tumor cells.
Our research group has been committed to isolating and discovering active polysaccharides with anti-tumor effects from fungal fermentation broth for a long time. Through extensive screening, we found that extracellular polysaccharides isolated from apple Alternaria fermentation broth have good anti-tumor activity, which reminds us that plant pathogens may be an important source of anti-tumor active polysaccharides. Fusarium graminearum, also known as Fusarium graminearum, can infect wheat, causing pink or orange red mold like substances to appear on the diseased ears, leading to plant scab. This study isolated for the first time the extracellular polysaccharides of Fusarium graminearum from its fermentation broth. After in vitro screening, it was found that FGEPS can significantly inhibit the proliferation of human gastric cancer cell line SGC7901. This article explores the in vitro anti gastric cancer SGC-7901 effect and mechanism of Fusarium graminearum extracellular polysaccharides, providing experimental basis for the development of anti gastric cancer active polysaccharide drugs.

 

Natural products have always been a treasure trove for pharmaceutical development, playing a huge role in disease treatment. In terms of anti-tumor effects, natural medicines such as paclitaxel, camptothecin, podophyllotoxin, vinblastine, etc. not only have practical effects, but also provide ideas and references for the synthesis of new compounds. The secondary metabolites during fungal fermentation are an important source of active polysaccharides. The extracellular polysaccharide EPS isolated from the fermentation broth of Rhizopus nigricans activates the AMP activated protein kinase (AMPK) pathway in mouse colon cancer CT26 cells, inhibiting cell growth and promoting apoptosis in a dose-dependent and time-dependent manner; The extracellular polysaccharides of Aspergillus niger increase the activity of Caspase-9 and Caspase-3 in a dose-dependent manner, increase the ratio of Bax/Bcl-2, promote the release of cytochrome C (Cyt-C) into the cytoplasm, and induce apoptosis in MCF-7 cells through the intrinsic mitochondrial apoptotic pathway; The extracellular polysaccharides of apple fungus can increase the level of reactive oxygen species in gastric cancer BGC-823 cells, reduce mitochondrial membrane potential, and form apoptotic bodies. The FGEPS that can effectively inhibit the proliferation of human gastric cancer cells SGC-7901 in this study was isolated from the fermentation broth of Fusarium graminearum. The CCK8 experiment showed that FGEPS can effectively inhibit the proliferation of human gastric cancer SGC-7901 cells. The morphological results showed that FGEPS can cause shrinkage and deformation of SGC-7901 cells, membrane foaming, and even the formation of apoptotic bodies, which are the manifestations of cell apoptosis. The results of AnexinVFITC/PI double staining, Hoechst33258 staining, and JC-1 staining indicate that FGEPS can induce apoptosis in SGC-7901 cells and may be related to mitochondrial mediated pathways. Due to the fact that apoptosis is a programmed cell death controlled by genes, involving the regulation of a series of genes, we investigated the role of mitochondrial pathway in FGEPS induced apoptosis of SGC-7901 cells based on relevant results.
Through exploring the mechanism of inducing apoptosis, we found that FGEPS can significantly upregulate the expression of pro apoptotic proteins Bax, Cleaved Caspase-3, and Cleaved Caspase-9, and downregulate the expression of anti apoptotic protein Bcl-2. This indicates that mitochondrial mediated cell apoptosis is closely related to the anti human gastric cancer SGC-7901 effect of FGEPS. Mitochondria mediated cell apoptosis mainly refers to the imbalance between the anti apoptotic protein Bcl-2 and the apoptotic protein family Bax ratio under the stimulation of apoptotic signals. Overexpression of Bax causes an increase in mitochondrial membrane permeability, releasing factors such as Cyt-C. After binding with the apoptotic protease activating factor, it can activate the apoptotic protease Caspase-9, promote the binding of cysteine aspartic acid, and form apoptotic bodies. Caspase is a large family of apoptotic proteases that can be activated through the mitochondrial pathway, and activated Caspase can also cause mitochondria to release more Cyt-C. The “waterfall” activation chain of this family will ultimately lead cells towards apoptosis. Caspase-9 is located at the top of the “waterfall” activation chain, and activated Caspase-9 will trigger the activation of downstream effector molecules such as Caspase-3, leading to a cascade reaction of Caspase and causing chromatin condensation, lysis, and separation from the cell body to form apoptotic bodies. This study found that FGEPS can induce apoptosis in SGC7901 cells, and the mitochondrial mediated apoptosis pathway plays an important role in the process of FGEPS induced apoptosis in gastric cancer SGC-7901 cells. Polysaccharides, as natural high molecular weight substances, are not only the basic components of structure and energy substances, but also key molecules involved in the regulation and response of the body. With the development of glycobiology, polysaccharides have become a research hotspot for anti-tumor drugs due to their excellent anti-tumor activity.
In summary, this study isolated the extracellular polysaccharide FGEPS from Fusarium graminearum for the first time. It has a proliferation inhibitory effect on SGC-7901, BGC-823, and MGC803, with the most significant inhibitory effect on SGC-7901. It can also induce apoptosis in SGC-7901 cells through the mitochondrial pathway. The experiment provides a basis for further exploring the anti gastric cancer effect of FGEPS and for developing polysaccharide based adjuvant therapy drugs for gastric cancer.

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