<i>Celastrus orbiculatus</i> Extract Inhibits the Invasion and Migration of Human Gastric
Cancer Cells in the Hypoxia Microenvironment

Feng, Guangqing; Chu, Zewen; Wang, Haibo; Liu, Yanqing; Zhu, Fangshi

doi:10.2174/1871520622666220421092831

Cited by 3 publications

(1 citation statement)

References 47 publications

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“…The extraction and use of the effective components of COE have been authorized by the national invention patent (Grant No: 200710025343.3). The previous research results showed that COE could inhibit EMT, invasion, and the metastasis of GC cells [15][16][17][18]. However, the main anti-GC components of COE are still being explored.…”

Section: Introductionmentioning

confidence: 99%

Triptonoterpene, a Natural Product from Celastrus orbiculatus Thunb, Has Biological Activity against the Metastasis of Gastric Cancer Cells

Wang

Luo²,

Hu³

et al. 2022

Molecules

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Cancer is one of the greatest threats to human health. Gastric cancer (GC) is the fifth most common malignant tumor in the world. Invasion and metastasis are the major difficulties in the treatment of GC. Herbal medicines and their extracts have a lengthy history of being used to treat tumors in China. The anti-tumoral effects of the natural products derived from herbs have received a great deal of attention. Our previous studies have shown that the traditional Chinese herb Celastrus orbiculatus Thunb extract (COE) can inhibit the invasion and metastasis of GC cells, but the specific anti-cancer components of COE are still unclear. Dozens of natural products from COE have been isolated and identified by HPLC spectroscopy in our previous experiments. Triptonoterpene is one of the active ingredients in COE. In this study, we focused on revealing whether Triptonoterpene has an excellent anti-GC effect and can be used as an effective component of Celastrus orbiculatus Thunb in the treatment of tumors. We first observed that Triptonoterpene reduces GC cell proliferation through CCK-8 assays and colony formation experiments. The cell adhesion assays have shown that Triptonoterpene inhibits adhesion between cells and the cell matrix during tumor invasion. In addition, the cell migration assay has shown that Triptonoterpene inhibits the invasion and migration of GC cells. The high-connotation cell dynamic tracking experiment has also shown the same results. The effects of Triptonoterpene on epidermal mesenchymal transition (EMT)-related and matrix metalloproteinases (MMPs)-related proteins in gastric cancer cells were detected by Western blots. We found that Triptonoterpene could significantly inhibit the changes in EMT-related and invasion and metastasis-related proteins. Altogether, these results suggest that Triptonoterpene is capable of inhibiting the migration and invasion of GC cells. Triptonoterpene, as a natural product from Celastrus orbiculatus Thunb, has significant anti-gastric cancer effects, and is likely to be one of the major equivalent components of Celastrus orbiculatus Thunb.

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Section: Introductionmentioning

confidence: 99%

Triptonoterpene, a Natural Product from Celastrus orbiculatus Thunb, Has Biological Activity against the Metastasis of Gastric Cancer Cells

Wang

Luo²,

Hu³

et al. 2022

Molecules

Self Cite

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Hypoxia exacerbates the malignant transformation of gastric epithelial cells induced by long-term H. pylori infection

He,

Zhang,

Zhang

et al. 2024

Microbiol Spectr

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Helicobacter pylori is a microaerophilic Gram-negative bacterium that resides in the human stomach and is classified as a class I carcinogen for gastric cancer. Numerous studies have demonstrated that H. pylori infection plays a role in regulating the function of host cells, thereby contributing to the malignant transformation of these cells. However, H. pylori infection is a chronic process, and short-term cellular experiments may not provide a comprehensive understanding of the in vivo situation, especially when considering the lower oxygen levels in the human stomach. In this study, we aimed to investigate the mechanisms underlying gastric cell dysfunction after prolonged exposure to H. pylori under hypoxic conditions. We conducted a co-culture experiment using the gastric cell line GES-1 and H. pylori for 30 generations under intermittent hypoxic conditions. By closely monitoring cell proliferation, migration, invasion, autophagy, and apoptosis, we revealed that sustained H. pylori stimulation under hypoxic conditions significantly influences the function of GES-1 cells. This stimulation induces epithelial-mesenchymal transition and contributes to the propensity for malignant transformation of gastric cells. To confirm the in vitro results, we conducted an experiment involving Mongolian gerbils infected with H. pylori for 85 weeks. All the results strongly suggest that the Nod1 receptor signaling pathway plays a crucial role in H. pylori -related apoptosis and autophagy. In summary, continuous stimulation by H. pylori affects the functioning of gastric cells through the Nod1 receptor signaling pathway, increasing the likelihood of cell carcinogenesis. The presence of hypoxic conditions further exacerbates this process. IMPORTANCE Deciphering the collaborative effects of Helicobacter pylori infection on gastric epithelial cell function is key to unraveling the development mechanisms of gastric cancer. Prior research has solely examined the outcomes of short-term H. pylori stimulation on gastric epithelial cells under aerobic conditions, neglecting the bacterium’s nature as a microaerophilic organism that leads to cancer following prolonged stomach colonization. This study mimics a more genuine in vivo infection scenario by repeatedly exposing gastric epithelial cells to H. pylori under hypoxic conditions for up to 30 generations. The results show that chronic exposure to H. pylori in hypoxia substantially increases cell migration, invasion, and epithelial-mesenchymal transition, while suppressing autophagy and apoptosis. This highlights the significance of hypoxic conditions in intensifying the carcinogenic impact of H. pylori infection. By accurately replicating the in vivo gastric environment, this study enhances our comprehension of H. pylori ’s pathogenic mechanisms in gastric cancer.

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Echium amoenum and Rosmarinic Acid Suppress the Growth and Metastasis of Gastric Cancer AGS Cells by Promoting Apoptosis and Inhibiting EMT

Ahmadi,

Kim,

Park

et al. 2024

IJMS

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Gastric cancer (GC) ranks as the fifth most prevalent cancer globally. Owing to the absence of early manifest symptoms, it is difficult to diagnose GC until it has metastasized to other organs. Hence, the prevention and treatment of GC have become major concerns for patients. Echium amoenum, a traditional medicinal plant from the Boraginaceae family, exhibits various biological activities. Although recent studies have reported the anticancer properties of E. amoenum, its effects and mechanisms of action on GC cells are not yet fully understood. This study examined the anticancer effects of the ethyl acetate extract of E. amoenum (EAEC) and its main active ingredient, rosmarinic acid (RA), in GC AGS cells. EAEC and RA suppressed AGS cell growth by inducing apoptosis through caspase mediation and inhibited AGS cell metastasis by influencing the expression of crucial epithelial–mesenchymal transition (EMT) biomarkers. Furthermore, the anti-growth and anti-metastatic effects of EAEC and RA on AGS cells involved inactivation of the STAT3, AKT, and ERK1/2 pathways. Additionally, RA notably inhibited the in vivo tumor growth in AGS cells. Overall, these results indicate that EAEC and RA could serve as potential anticancer and anti-metastasis agents for GC.

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Celastrus orbiculatus Extract Inhibits the Invasion and Migration of Human Gastric Cancer Cells in the Hypoxia Microenvironment

Cited by 3 publications

References 47 publications

Triptonoterpene, a Natural Product from Celastrus orbiculatus Thunb, Has Biological Activity against the Metastasis of Gastric Cancer Cells

Triptonoterpene, a Natural Product from Celastrus orbiculatus Thunb, Has Biological Activity against the Metastasis of Gastric Cancer Cells

Hypoxia exacerbates the malignant transformation of gastric epithelial cells induced by long-term H. pylori infection

Echium amoenum and Rosmarinic Acid Suppress the Growth and Metastasis of Gastric Cancer AGS Cells by Promoting Apoptosis and Inhibiting EMT

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