The Synergistic Cytotoxic Effect of Pentagamavunon-1 (PGV-1) and Curcumin Correlates with the Cell Cycle Arrest to Induce Mitotic Catastrophe in 4T1 and T47D Breast Cancer Cells

BACKGROUND: The anti-cancer properties of pentagamavunon-1 (PGV-1) and curcumin have been documented. This study aimed to evaluate the cytotoxic effect of this combination on breast cancer cell growth using 4T1 and T47D cells, representing triple-negative breast cancer (TNBC) and non-TNBC, respectively. METHODS: Cytotoxic assay was evaluated using MTT reagent for single and combination treatment of PGV-1 and curcumin in 4T1 and T47D cells. Cell cycle analysis was examined through flowcytometry with propidium iodide dye. May Grünwald-Giemsa staining was also performed to analyze the mitotic catastrophe RESULTS: PGV-1 and curcumin alone had significant cytotoxic effects against two breast cancer cell lines, with IC50 values of 4 μM and 40 μM for 4T1 and 2 μM and 20 μM for T47D, respectively. Both compounds showed high selectivity for the 4T1 and T47D cells (selectivity index >3). In addition, when PGV-1 and curcumin were combined, a synergistic effect was observed in both cell types with a combination index of <0.7. This combination results in cell cycle arrest in the G2/M phase, increased cell accumulation in the sub-G1 phase, and a synergistic increase in mitotic catastrophe. CONCLUSION: Combined intervention of PGV-1 and curcumin on TNBC and non-TNBC breast cancer cells substantially augments cell cycle arrest in the G2/M and sub-G1 phases, coupled with the occurrence of mitotic catastrophe. In summary, the results suggest that PGV-1 coupled with curcumin holds promise as an effective approach to addressing breast cancer and warrants further investigation.