Background: Triple-negative breast Cancer (TNBC) is one of the challenges of the breast cancer (BC) field. Ganoderma lucidum (GL) has been studied in the last decades for anticancer activity also whole extracts were proposed as a potential targeting therapy for inhibiting Invasive Breast Cancer (IBC). However, concrete regulatory mechanisms on cancer hallmarks and autophagy have remained unclear.
Result: We aim to study the anti-cancer activities of GL, to illustrate the main mechanisms of anti-Hallmark activity of the extracts on Ras-addicted invasive TNBC model cell-line (MDA-MB-231) by using High-throughput Gene Expression Profiling (GEP) via Next-Generation Sequencing (NGS). So, in this study, MDA cells were treated with GL ethanolic extracts (GLE), to extract the total RNA for NGS, and several standard pre-clinical cellular tests (MTT, DAPI, Cell Cycle, and Annexin V/PI apoptosis assay) were implemented. Accordingly, GLE has strong effectivity on the MDA cells in all molecular hallmarks and cellular experiments. We demonstrated that GLE induces autophagy through the Ferroptosis pathway. GLE caused the cell cycle to be arrested in the G0 phase and Ras addiction was inhibited through MAPK. Also, VEGFR, genome instability, and central carbon metabolism pathways inhibition were recognized in treated MDA cells GEP. In conclusion, GLE can take all the kill marks of cancer hallmarks. The evidence shows that some natural compounds can act with wide-hallmark effectivity and specificity, like selective Antibiotics for Cancer. We found out the forgotten key of the king of the herbs from Traditional Chinese Medicine against Cancer is ferroptosis which causes autophagy, which forces cancerous cells to perform Homeostasis as the ultimate weapon against Cancer.