Sarmoko Sarmoko, Novitasari Dhania, Toriyama Manami, Fareza Muhamad Salman, Choironi Nur Amalia, Itoh Hiroshi, Meiyanto Edy
Department of Pharmacy, Sumatera Institute of Technology, Lampung, Indonesia.
Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Indonesia.
Iran J Pharm Res. 2023 Nov 10;22(1):e138856. doi: 10.5812/ijpr-138856. eCollection 2023 Jan-Dec.
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.
This study was performed to analyze and compare different modes of action of γ-mangostin and α-mangostin as antimigratory effects targeted on in MDA-MB-231 as a model of TNBC cell.
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.
The findings revealed half maximal inhibitory concentration (IC50) values of 25 and 20 μM for γ-mangostin and α-mangostin in MDA-MB 231 cells, respectively. Moreover, a concentration of 10 μM 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 , CXCR4, and , 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 in high affinity.
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 mRNA expression that might correlate to its activity to inhibit MDA-MB-231 cell migration.
两种山竹素化合物，γ-山竹素和α-山竹素，通过抑制细胞增殖和细胞迁移显示出抗癌特性。转移性三阴性乳腺癌（TNBC）细胞，包括MDA-MB-231，高表达C-X-C趋化因子受体4（CXCR4）以维持活性氧（ROS）和细胞迁移。
本研究旨在分析和比较γ-山竹素和α-山竹素作为针对TNBC细胞模型MDA-MB-231的抗迁移作用的不同作用模式。
本研究使用一系列检测方法研究γ-山竹素和α-山竹素的作用，包括用于细胞毒性检测的细胞计数试剂盒-8（CCK-8）检测、用于迁移研究的伤口愈合检测、用于基因表达分析的定量实时聚合酶链反应（qRT-PCR）以及用于ROS测量的流式细胞术，同时进行计算机模拟研究以观察化合物与CXCR4之间的结合。
研究结果显示，γ-山竹素和α-山竹素在MDA-MB 231细胞中的半数最大抑制浓度（IC50）值分别为25和20μM。此外，迁移检测使用的浓度为10μM。γ-山竹素和α-山竹素在24小时内均显著抑制细胞迁移。目前的基因表达研究显示，γ-山竹素处理后关键迁移相关基因即CXCR4和[此处原文缺失基因名称]下调，但α-山竹素处理后未下调。此外，γ-山竹素和α-山竹素均增加细胞内ROS生成，突出了γ-山竹素和α-山竹素升高ROS对抑制癌细胞迁移的相同作用。分子对接模拟进一步表明γ-山竹素和α-山竹素与[此处原文缺失相关蛋白名称]具有高亲和力的潜在相互作用。
这些发现表明，γ-山竹素和α-山竹素均抑制MDA-MB-231细胞中的乳腺癌细胞迁移并诱导细胞ROS水平；值得注意的是，γ-山竹素抑制[此处原文缺失基因名称]mRNA表达，这可能与其抑制MDA-MB-231细胞迁移的活性相关。
