The Growth Suppression Activity of Diosmin and PGV-1 Co-Treatment on 4T1 Breast Cancer Targets Mitotic Regulatory Proteins

Musyayyadah, Hajidah and Wulandari, Febri and Nangimi, Ana Fiin and Anggraeni, Afivah Dewi and Ikawati, Muthi and Meiyanto, Edy (2021) The Growth Suppression Activity of Diosmin and PGV-1 Co-Treatment on 4T1 Breast Cancer Targets Mitotic Regulatory Proteins. Asian Pacific Journal of Cancer Prevention, 22 (9). 2929 – 2938. ISSN 15137368

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Abstract

Objective: We aim to enhance the effectiveness of curcumin analog PGV-1 through co-treatment with diosmin, a citrus flavonoid, on 4T1 cells and evaluate the molecular targets underlying its effect on the cell cycle. Methods: Cytotoxic effects were performed by MTT assay against 4T1 cells. The May Grünwald-Giemsa staining was used to observe cell cycle arrest. The senescence was assayed with SA-ß-gal staining. Bioinformatic studies were utilized to discover protein targets of PGV-1 and diosmin on triple-negative breast cancer (TNBC) using SwissTargetPrediction, then exploration of protein targets was performed using the TCGA dataset via the UALCAN website. Kaplan-Meier was performed using GraphPad with data from the TCGA dataset via Oncoln. Using MOE 2010, we conducted the binding affinity between PGV-1 and diosmin to protein targets. Results: PGV-1 and diosmin showed cytotoxic effect with IC50 values of 9 μM and 389 μM, respectively, and the combined cytotoxic assay exhibited a synergistic effect with a combination index (CI) of <1. PGV-arrested 4T1 cells in pro-metaphase and induced mitotic catastrophe, while the combination of diosmin with PGV-1 increased the number of mitotic catastrophes. The SA-ß-gal assay revealed that both compounds were capable of inducing senescence in 4T1 cells. Study bioinformatics and molecular docking showed that PGV-1 and diosmin target cell cycle regulatory proteins in TNBC, namely CDK1, KIF11, and AURKA. Thus, the combination of diosmin and PGV-1 modulating the cell cycle that causes senescence and catastrophic death of 4T1 cancer cells is related to the inhibition of these cell cycle proteins. Conclusion: Diosmin enhances the cytotoxic effect of PGV-1 synergistically on 4T1 cancer cells, which correlates to the increasing senescence and mitotic catastrophe. The synergistic effect of the co-treatment is likely to target AURKA, CDK1, and KIF11. The combination of PGV-1 and diosmin performs a potential as a combinatorial anticancer drug for TNBC. © This work is licensed under a Creative Commons Attribution-Non Commercial 4.0 International License

Item Type: Article
Additional Information: Cited by: 13; All Open Access, Gold Open Access
Uncontrolled Keywords: Co-treatment diosmin and PGV-1; 4T1; Mitotic catastrophe; Mitotic regulatory proteins; Senescence
Subjects: R Medicine > RS Pharmacy and materia medica
Divisions: Faculty of Pharmacy
Depositing User: Sri JUNANDI
Date Deposited: 26 Sep 2024 07:05
Last Modified: 26 Sep 2024 07:07
URI: https://ir.lib.ugm.ac.id/id/eprint/4612

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