Objective: This study aimed to evaluate the anticancer activity of cryptotanshinone (CPT) in estrogen and progesterone receptor-positive (ER+/PR+) MCF-7 breast cancer cells and to determine whether delivery via the filamentous M13 bacteriophage enhances CPT’s functional effect, with a focus on FOXM1 gene expression.

Materials and Methods: MCF-7 cells were treated with CPT across a concentration range to establish dose-response behavior and calculate IC₅₀ values at 24 and 48 h using an MTT viability assay. For phage-mediated delivery, cells were exposed to M13 alone, free CPT, CPT co-administered with M13 without loading, and preformed M13–CPT complexes, followed by MTT-based viability assessment. FOXM1 messenger ribonucleic acid (mRNA) levels were quantified at 24 and 48 h by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and normalized to a housekeeping gene using ΔCt-based analysis.

Results: CPT decreased cell viability in a dose- and time-dependent manner, yielding IC₅₀ values of 19.82 μM at 24 h and 16.14 μM at 48 h. CPT also suppressed FOXM1 expression, with a stronger inhibitory effect at 48 h rather than at 24 h. M13 alone did not produce a meaningful change in viability. Compared with free CPT and the non-loaded CPT+M13 mixture, M13–CPT induced a markedly greater reduction in cell viability. In addition, Annexin V-fluorescein isothiocyanate/propidium iodide (V-FITC/PI) analysis showed that CPT increased apoptosis, with a stronger effect in the M13–CPT group than free CPT.

Conclusions: CPT reduces MCF-7 cell viability and downregulates FOXM1 expression, and delivery through M13 bacteriophage further enhances in vitro cytotoxic efficacy without requiring additional targeting ligands.