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.
Highlights
Gastric cancer is one of the world’s leading causes of cancer-associated death, with a minimum survival rate of five years after diagnosis [1]
Our results showed an increase in the expression level of Beclin1 and Atg14 when treated with LP1 which further supports the induction of autophagy (Figure 3(D1,D5))
We found that LP1 significantly suppressed the expression level of Matrix metalloproteinases (MMPs)-2 from 96.6% to 31.0% and MMP-9 from 81.9 to 36.13% (Figure 4(C1,C2)) which in turn leads to significantly reduced rate of wound healing, migration and invasion in SGC-7901 cells
Summary
Gastric cancer is one of the world’s leading causes of cancer-associated death, with a minimum survival rate of five years after diagnosis [1]. In 60% of the cases, Helicobacter pylori has been reported to be the main culprit, while in rest of the cases several lifestyle (smoking, dietary habits, obesity) associated and genetic factors are involved [6]. It takes several years for the development of stomach cancer initial symptoms including anorexia, dyspepsia, weight loss and abdominal discomfort are mostly ignored by the patients [7]. Diagnosis of gastric cancer is very crucial, as in the advanced stages treatment is difficult because of the metastasis which leads the degradation of extracellular matrix, epithelial-to-mesenchymal transition and abnormalities in programmed cell death [8]. Chemotherapy is considered as an alternative method for the treatment of gastric cancer in clinical applications, drug resistance and toxicity are the main hurdles [10]
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