Latcripin-7A, derivative of Lentinula edodes C91-3, reduces migration and induces apoptosis, autophagy, and cell cycle arrest at G1 phase in breast cancer cells.

Due to the high mortality rate and an increase in breast cancer incidence, it has been challenging for researchers to come across an effective chemotherapeutic strategy with minimum side effects. Therefore, the need for the development of effective chemotherapeutic drugs is still on the verge. Consequently, we approached a new mechanism to address this issue. The naturally available peptide named latcripin-7A (LP-7A), extracted from a mushroom called Lentinula edodes, provided us promising results in terms of growth arrest, apoptosis, and autophagy in breast cancer cells (MCF-7 and MDA-MB-231). Expressions of protein markers for apoptosis, autophagy, and cell cycle were confirmed via Western blot analysis. Migration and invasion assays were performed to analyze the anti-migratory and anti-invasive properties of LP-7A, while cell cycle analysis was performed via flow cytometry to evaluate its affect over cell growth. Supportive assays were performed like acridine orange, Hoechst 33258 stain, DNA fragmentation, and mitochondrial membrane potential (MMP) to further confirm the anticancer effect of LP-7A on breast cancer cell lines. It is concluded that LP-7A effectively reduces migration and promotes apoptosis as well as autophagy in MCF-7 and MDA-MB-231 breast cancer cell lines by inducing cell growth arrest at G0/G1 phase and decreasing mitochondrial membrane potential without adverse effects on MCF-10A normal breast cells. KEY POINTS: • In this study, we have investigated the anti-cancer activity of novel latcripin-7A (LP-7A), a protein extracted as a result of de novo characterization of Lentinula edodes C91-3. • We conclude in our research work that LP-7A can initiate diverse cell death-related events, i.e., apoptosis and autophagy in both triple-positive and triple-negative breast cancer cell lines by interacting with different nodes of cellular signaling that can further be investigated in vivo to gain a better understanding.

LP1 from Lentinula edodes C91-3 Induces Autophagy, Apoptosis and Reduces Metastasis in Human Gastric Cancer Cell Line SGC-7901.

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.