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
Full text not available from this repository. (Request a copy)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 |
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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 |