Different Modes of Mechanism of Gamma-Mangostin and Alpha-Mangostin to Inhibit Cell Migration of Triple-Negative Breast Cancer Cells Concerning CXCR4 Downregulation and ROS Generation

Sarmoko, Sarmoko and Novitasari, Dhania and Toriyama, Manami and Fareza, Muhamad Salman and Choironi, Nur Amalia and Itoh, Hiroshi and Meiyanto, Edy (2023) Different Modes of Mechanism of Gamma-Mangostin and Alpha-Mangostin to Inhibit Cell Migration of Triple-Negative Breast Cancer Cells Concerning CXCR4 Downregulation and ROS Generation. Iranian Journal of Pharmaceutical Research, 22 (1): e138856. ISSN 17350328

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Different Modes of Mechanism of Gamma-Mangostin and Alpha-Mangostin to Inhibit Cell Migration of Triple-Negative Breast Cancer Cells Concerning CXCR4 Downregulation and ROS Generation.pdf
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Abstract

Background: Two mangostin compounds, gamma-mangostin and alpha-mangostin, show anticancer properties through the inhibition of cell proliferation and cell migration. Metastatic triple-negative breast cancer (TNBC) cells, including MDA-MB-231, highly express C-X-C chemokine receptor type 4 (CXCR4) to maintain reactive oxygen species (ROS) and cell migration. Objectives: This study was performed to analyze and compare different modes of action of γ-mangostin and α-mangostin as antimigratory effects targeted on CXCR4 in MDA-MB-231 as a model of TNBC cell. Methods: This study investigated the effect of γ-mangostin and α-mangostin using a series of assays, including Cell Counting Kit- 8 (CCK-8) assay for cytotoxicity, wound healing assay for migration study, quantitative real-time polymerase chain reaction (qRT-PCR) for gene expression analysis, and flow cytometry for ROS measurement, along with in silico study to observe the binding between the compound and CXCR4. Results: The findings revealed half maximal inhibitory concentration (IC50) values of 25 and 20μM for γ-mangostin and α-mangostin in MDA-MB 231 cells, respectively. Moreover, a concentration of 10μM was used for the migration assay. Both γ-mangostin and α-mangostin significantly suppressed cell migration within 24 hours. The present gene expression studies revealed the downregulation of key migration-associated genes, namely Farp, CXCR4, and LPHN2, upon γ-mangostin treatment but not α-mangostin. Additionally, both γ-mangostin and α-mangostin increased cellular ROS generation, highlighting the same effect of γ-mangostin and α-mangostin ROS elevation to inhibit cancer cell migration. Molecular docking simulations further suggested a potential interaction between γ-mangostin and α-mangostin with CXCR4 in high affinity. Conclusions: These findings suggest that both γ-mangostin and α-mangostin inhibit breast cancer cell migration and induce cellular ROS levels in MDA-MB-231 cells; notably, γ-mangostin suppresses CXCR4 mRNA expression that might correlate to its activity to inhibit MDA-MB-231 cell migration. © 2023, Brieflands. All rights reserved.

Item Type: Article
Additional Information: Cited by: 1; All Open Access, Hybrid Gold Open Access
Uncontrolled Keywords: alpha mangostin plant extract; antineoplastic agent; chemokine receptor CXCR4; gamma mangostin plant extract; plant extract; Rac1 protein; reactive oxygen metabolite; unclassified drug; Article; bioinformatics; cell migration; cell viability; clinical trial; controlled clinical trial; controlled study; cytotoxicity assay; farp gene; flow cytometry; Garcinia mangostana; human; human cell; IC50; LPHN2 gene; MDA-MB-231 cell line; migration inhibition; molecular docking; mRNA expression level; real time polymerase chain reaction; triple negative breast cancer; wound healing assay
Subjects: R Medicine > RB Pathology
Divisions: Faculty of Medicine, Public Health and Nursing > Biomedical Sciences
Depositing User: Ani PURWANDARI
Date Deposited: 16 May 2024 02:23
Last Modified: 16 May 2024 02:23
URI: https://ir.lib.ugm.ac.id/id/eprint/1176

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