Renieramycin M Sensitizes Anoikis-resistant H460 Lung Cancer Cells to Anoikis

Anoikis resistance plays a crucial role in the promotion of survival of circulating tumor cells. This study aimed to evaluate the mechanistic pathways of anoikis resistance in human lung cancer cells and test the possible therapeutic effect of renieramycin M (RM) from the sponge Xestospongia sp. in conversion of anoikis resistance.Anoikis-resistant H460 (AR_H460) lung cancer cells in a detached condition were treated with RM at subtoxic concentrations for 24 h. Cell viability, cell morphology, and expression of the proteins involved in survival and apoptotic pathways were determined.Anoikis resistance in H460 cells is mediated through the up-regulation of survival and anti-apoptotic proteins, namely phosphorylated extracellular signal-regulated kinase (p-ERK), phosphorylated ATP-dependent tyrosine kinase (p-AKT), B-cell lymphoma-2 (BCL2), and myeloid cell leukemia-1 (MCL1). RM significantly reduced cell viability and inhibited spontaneous aggregation of AR_H460 cells. Western blot analysis revealed that RM suppressed the levels of survival proteins p-ERK and p-AKT and anti-apoptotic proteins BCL2 and MCL1.RM is a potential anti-metastatic agent by sensitizing anoikis-resistant lung cancer cells to anoikis by the suppression of anoikis-resistance mechanisms.