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Potential Targets in Innate Immunity Receptors for Gastric Cancer: Insights from Virtual Screening in TCM and In
Abbas Ganjali1, Baratali Fakheri2, Abbas Bahari3
1University of Zabol, Zabol, Iran.
Background:
Gastric Cancer (GC) poses a substantial global health threat, ranking as the second leading cause of cancer-related mortality among gastrointestinal malignancies. This investigation explores the potential therapeutic implications of plant extracts on gastric cancer, with a specific focus on their effects on the innate immune system.
Methods:
A comprehensive analysis was conducted using 200 Sequence Read Runs (SRRs) thigh samples associated with gastrointestinal cancer tissue, juxtaposed with pathologically confirmed healthy tissues serving as controls. Differential Gene Expression (DGE) testing, encompassing the examination of 28,000 genes, including 95 pivotal genes associated with the innate immune system, was conducted. Findings elucidate alterations in the expression of key pattern recognition receptors, such as TLR2 and TLR4, as well as pivotal molecules within their signaling pathways. In pursuit of potential antagonists for these receptors, virtual screening on the Maestro docking platform in the Schrödinger 2022 package was conducted, evaluating 220,000 diverse tautomer's of plant active substances. Selected candidates, exhibiting superior docking scores across four additional platforms, were subjected to further scrutiny.
Results:
MMT results showed that nettle extract showed significant cytotoxic effects within 12 hr compared to the control (no treatment) sample, resulting in a 34.7% reduction in AGS cancer cell viability. The flow cytometry test showed that the control group had 71%, and groups treated with nettle extract for two and 12 hr had 65.3 and 67.18% viable cells, respectively. These differences were not statistically significant, indicating that nettle extract selectively preserves healthy living cells.
Conclusion:
Cytotoxicity tests and cell cycle assessments confirmed the ability of nettle extract to reduce the survival of GC cells. This property makes nettle a promising candidate for drug development in this direction.
Insights
Nettle extract demonstrates significant cytotoxic effects against gastric cancer cells, reducing viability by 34.7%. This plant-derived compound shows promise for developing new gastric cancer therapies by targeting cancer cells while preserving healthy ones.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Gastric cancer (GC) is a leading cause of cancer mortality globally.
- This study investigates plant extracts' therapeutic potential against GC, focusing on the innate immune system.
Purpose of the Study:
- To explore the impact of plant extracts on gastric cancer cells.
- To identify potential therapeutic agents targeting innate immune pathways in GC.
Main Methods:
- Analyzed gene expression in 200 gastrointestinal cancer tissue samples versus healthy controls.
- Performed virtual screening of 220,000 plant compounds against innate immune receptors (TLR2, TLR4).
- Assessed nettle extract's cytotoxicity and cell viability using MTT and flow cytometry.
Main Results:
- Nettle extract reduced AGS gastric cancer cell viability by 34.7% within 12 hours.
- Flow cytometry indicated nettle extract selectively preserved healthy cells, with no significant reduction in viability.
- Differential gene expression revealed alterations in innate immune receptors and signaling pathways.
Conclusions:
- Nettle extract exhibits significant cytotoxicity against gastric cancer cells.
- Nettle extract demonstrates selective toxicity, preserving healthy cells.
- Nettle shows promise as a potential therapeutic agent for gastric cancer drug development.
