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LP1 from Lentinula edodes C91-3 Induces Autophagy, Apoptosis and Reduces Metastasis in Human Gastric Cancer Cell Line
Samana Batool1, Thomson Patrick Joseph2, Mushraf Hussain3
1Department of Microbiology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China. samana.batool12@yahoo.com.
Abstract:
Present study aimed to elucidate the anticancer effect and the possible molecular mechanism underlying the action of Latcripin 1 (LP1), from the mushroom Lentinula edodes strain C91-3 against gastric cancer cell lines SGC-7901 and BGC-823. Cell viability was measured by Cell Counting Kit-8 (CCK-8); morphological changes were observed by phase contrast microscope; autophagy was determined by transmission electron microscope and fluorescence microscope. Apoptosis and cell cycle were assessed by flow cytometer; wound-healing, transwell migration and invasion assays were performed to investigate the effect of LP1 on gastric cancer cell's migration and invasion. Herein, we found that LP1 resulted in the induction of autophagy by the formation of autophagosomes and conversion of light chain 3 (LC3I into LC3II. LP1 up-regulated the expression level of autophagy-related gene (Atg7, Atg5, Atg12, Atg14) and Beclin1; increased and decreased the expression level of pro-apoptotic (Bax) and anti-apoptotic (Bcl-2) proteins respectively, along with the activation of Caspase-3. At lower-doses, LP1 have shown to arrest cells in the S phase of the cell cycle and decreased the expression level of matrix metalloproteinase MMP-2 and MMP-9. In addition, it has also been shown to regulate the phosphorylation of one of the most hampered gastric cancer pathway, that is, protein kinase B/mammalian target of rapamycin (Akt/mTOR) channel and resulted in cell death. These findings suggested LP1 as a potential natural anti-cancer agent, for exploring the gastric cancer therapies and as a contender for further in vitro and in vivo investigations.
Insights
Latcripin 1 (LP1) from mushrooms induces autophagy and apoptosis in gastric cancer cells. This natural compound shows potential as an anti-cancer agent by regulating cell death pathways and inhibiting migration.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Gastric cancer remains a significant global health challenge, necessitating novel therapeutic strategies.
- Natural products are a promising source for discovering new anti-cancer agents.
- Latcripin 1 (LP1) from *Lentinula edodes* mushroom presents a potential candidate for gastric cancer treatment.
Purpose of the Study:
- To investigate the anti-cancer effects of Latcripin 1 (LP1) on gastric cancer cell lines.
- To elucidate the molecular mechanisms underlying LP1's action, including autophagy, apoptosis, and cell cycle regulation.
- To assess LP1's impact on gastric cancer cell migration and invasion.
Main Methods:
- Cell viability assays (CCK-8) and morphological observation.
- Autophagy assessment using transmission electron microscopy and fluorescence microscopy.
- Flow cytometry for apoptosis and cell cycle analysis.
- Wound-healing, Transwell migration, and invasion assays.
- Western blotting to analyze protein expression (autophagy-related genes, apoptosis markers, MMP-2/9, Akt/mTOR pathway).
Main Results:
- LP1 induced autophagy, evidenced by autophagosome formation and LC3I/LC3II conversion.
- LP1 upregulated autophagy-related genes (Atg7, Atg5, Atg12, Atg14, Beclin1) and promoted apoptosis via Bax/Bcl-2 modulation and Caspase-3 activation.
- LP1 caused S-phase cell cycle arrest, decreased MMP-2/MMP-9 expression, and regulated the Akt/mTOR pathway.
- LP1 inhibited gastric cancer cell migration and invasion.
Conclusions:
- Latcripin 1 (LP1) exhibits significant anti-cancer properties against gastric cancer cells through the induction of autophagy and apoptosis.
- LP1 modulates key molecular pathways, including cell cycle regulation, matrix metalloproteinase activity, and the Akt/mTOR signaling pathway.
- LP1 demonstrates potential as a natural anti-cancer therapeutic agent for gastric cancer, warranting further in vitro and in vivo investigation.
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