Abstract

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.

Key words: PGV-1 (pentagamavunon-1), tamoxifen, 4-hydroxytamoxifen, co-chemotherapy, MCF-7 and T47D luminal breast cancer cell