Abstract
Pentagamavunon-1 (PGV-1), a potential chemopreventive agent with a strong cytotoxic effect, modulates prometaphase arrest. Improvement to get higher effectiveness of PGV-1 is a new challenge. A previous study reported that the natural compound, galangin, has antiproliferative activity against cancer cells with a lower cytotoxicity effect. This study aims to develop a combinatorial treatment of PGV-1 and galangin as an anticancer agent with higher effectiveness than a single agent. In this study, 4T1, a TNBC model cell, was treated with a combination of PGV-1 and galangin. As a result, PGV-1 and galangin showed a cytotoxic effect with IC50 values of 8 and 120 µM, respectively. Combining those chemicals has a synergistic impact, as shown by the combination index (CI) value of 1. Staining with the May Grunwald-Giemsa reagent indicated mitotic catastrophe evidence, characterized by micronuclear and multinucleated morphology. Moreover, the senescence percentage was higher than the single treatment. Furthermore, bioinformatics investigations showed that PGV-1 and galangin target CDK1, PLK1, and AURKB, overexpression proteins in TNBC that are essential in regulating cell cycle arrest. In conclusion, the combination of PGV-1 and galangin exhibit a synergistic effect and potential to be a chemotherapeutic drug by the mechanism of mitotic catastrophe and senescence induction.
Highlights
The National Cancer Institute has tested about 3000 plant species for anticancer therapeutic potential [1]
Cells were incubated in the absence and presence of PGV-1 (0.5–16 μM concentration) and galangin (10–1000 μM concentration), resulting in suppression of viable cells depending on the solution concentration (Figure 1a,b)
The antiproliferative activity was expressed in IC50, respectively, as the IC50 value of galangin and PGV-1 on 4T1 cells was 120 and 8 μM (Table 1)
Summary
Galangin restrains the proliferation of various types of cancer cells through a variety of pathways. Galangin elicits cell death in the ovarian cancer cells models, namely A2780/CP70 and OVCAR-3 [3]. Galangin-induced apoptosis could be initiated by increasing ROS generation. Galangin inhibits cancer cell cycle progression by downregulating cell cycle proteins machinery [4]. Galangin treatment on LuminalA breast cancer cell MCF-7 and T47D resulting in lowering cell population. Apoptosis on those cells was characterized by the increasing CL-caspase 3, CL-caspase 9, and Bax protein. Galangin regulated cell-cycle-associated proteins, causing cell cycle arrest in MCF-7 cells. Galangin performs the advantage of being selective for normal cells [5]
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