<![CDATA[Breast cancer stem cells (bCSCs) exhibit high plasticity, therapeutic resistance and immune evasion, making them critical targets for effective cancer immunotherapy. Pentagamavunone-1 (PGV-1), a curcumin analog, and its derivative, Chemoprevention Curcumin Analog-1.1 (CCA-1.1), possess cytotoxic and reactive oxygen species (ROS)-modulating properties. However, their potential role in modulating immune-related phenotypes in bCSCs remains unclear. In the study, bCSCs derived from the MDA-MB-231 cell line were treated with PGV-1 or CCA-1.1 to evaluate cytotoxicity, apoptosis, cell cycle distribution, stemness-associated markers and immune checkpoint expression. Cell viability was assessed using the CCK-8 assay. Apoptotic, stemness and immune-checkpoint profiles were analyzed using flow cytometry. PGV-1 exhibited stronger cytotoxicity against bCSCs than CCA-1.1, characterized by lower IC50 values (10.70 and 28.78 µM for PGV-1 and CCA-1.1 respectively at 24 h) and greater induction of apoptosis in a dose-dependent manner. Both compounds at concentrations of 2.67 and 7.19 µM significantly (p < 0.001) induced G2/M cell cycle arrest and reduced the CD44+CD24– stem-like population, indicating loss of stemness and enhanced differentiation. Importantly, PGV-1 significantly downregulated PD-L1 while upregulating CD80, suggesting a shift toward immunophenotypic alterations associated with a potentially more immunogenic profile. These dual effects of cytotoxic and preliminary immunophenotypic modulation highlight the ability of PGV-1 to overcome immune resistance in bCSCs. Further investigation using immune cell–based functional assays or in vivo models is required to validate whether the observed immunophenotypic modulation translates into functional immune activation and to assess the potential of PGV-1 in a co-immunotherapy setting.]]>
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