Persistent synergistic antiproliferative and apoptosis induction effects of PGV-1 and tamoxifen or 4-hydroxytamoxifen on ER-positive breast cancer cells

Tamoxifen (TAM) and its active metabolite, 4-hydroxytamoxifen (4-OHT), are major components of estrogen receptor (ER)-positive breast cancer treatment, but their efficacy is often limited by resistance and side effects. Pentagamavunone-1 (PGV-1), a curcumin analog, has demonstrated promising anticancer properties, suggesting its potential as a co-chemotherapy agent. This study evaluated the synergistic anticancer effects of PGV-1 in combination with TAM or 4-OHT on T47D and MCF-7 luminal breast cancer cells to enhance treatment efficacy and address resistance issues. The experimental design included cytotoxicity assays, washout persistent cytotoxicity assays, colony-formation tests, and cell cycle analysis using flow cytometry. Data were analyzed via ANOVA and post hoc Tukey HSD tests (α =.05). PGV-1, TAM, and 4-OHT individually showed potent cytotoxic effects on T47D and MCF-7 cells (IC50 < 10 μM) with minimal toxicity to normal cells. Combination treatments demonstrated significant synergy (combination index < 0.9) and persistent cytotoxicity, particularly for PGV-1 combined with 4-OHT, which strongly inhibited cancer cell colony formation. Cell cycle analysis revealed enhanced apoptosis, indicated by increased accumulation of cells in the sub-G1 phase (p < 0.001). Overall, combining PGV-1 with TAM or 4-OHT exhibited robust and sustained anticancer effects, presenting a promising luminal A breast cancer therapy strategy. © 2025 Desty Restia Rahmawati et al. This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).