Proteomic profiling reveals selaginellin A-induced blockade of cell cycle in MDA-MB-231 cells.

Abstract

Selaginellin A (Sela A), a derivative from Selaginella tamariscina, exerts anti-triple-negative breast cancer effects in MDA-MB-231 cells. Proteomic profiling identified 1 136 differentially expressed proteins (DEPs) after Sela A treatment, predominantly downregulated (n = 889). Enrichment analyses revealed Sela A significantly downregulated pathways critical for DNA repair, replication, and cell cycle progression, while upregulating ribosomal biogenesis and protein processing. Mechanistically, Sela A acts as a PTP1B inhibitor (IC50 = 7.4 μM), binding key residues (PHE-182, GLU-186). This inhibition activates the mechanistic target of rapamycin complex 1 (mTOR). Consequently, mTOR activation stimulates ribosomal synthesis but concurrently triggers a p70S6K-mediated negative feedback loop, degrading IRS1. IRS1 loss suppresses Akt signaling, reducing expression of cell cycle proteins and inducing G1-phase arrest. Thus, Sela A may block MDA-MB-231 cell proliferation via PTP1B inhibition driving mTOR/IRS1/Akt dysregulation.