National Innovation and Attracting Talents "111" base, Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, China.
Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Chongqing Engineering Research Center of Antitumor Natural Drugs, Chongqing Three Gorges Medical College, Chongqing 400030, China.
Food Funct. 2021 Nov 29;12(23):12036-12046. doi: 10.1039/d1fo02111g.
Diosmetin (DSM), a newly discovered natural flavonoid, found in citrus plants and olive leaves, has been reported to inhibit the progression of cancer when used as a food supplement. This study aimed to investigate DSM's anti-hepatocellular carcinoma (HCC) properties and possible molecular mechanisms. Hep3B and HCCLM3 cells were selected to evaluate the anti-HCC properties of DSM . RNA sequencing (RNA-seq) was used to identify the possible molecular targets and pathways. Gas chromatography-mass spectrometry (GC-MS) was used to evaluate the effect of DSM treatment on the primary metabolites of HCCLM3 cells. Tumor xenograft was performed in nude mice to examine the anti-HCC properties of DSM . The results showed that DSM inhibited the proliferation and migration of HCC cells in a dose-dependent manner. RNA-seq identified 4459 differentially expressed genes (DEGs) that were highly enriched in the cell cycle pathway. In addition, DSM regulated cell growth by arresting the cell cycle in the G1 phase by decreasing the expression of BCL2, CDK1, and CCND1. Furthermore, metabolomics analysis revealed that DSM interfered with the lipid metabolism pathway of HCC cells by significantly inhibiting the synthesis of metabolites, such as acetic acid, decanoic acid, glycerol, and L-proline. Subcutaneous tumor formation experiments revealed that DSM significantly reduced the tumor volume and weight when compared to the control. Immunohistochemical analysis further revealed that DSM treatment significantly decreased the expression of the proliferative marker KI67. Our findings demonstrated that DSM exhibited antitumor effects on HCC cells by inhibiting cell proliferation cell cycle arrest and interfering with lipid metabolism.
地奥司明（DSM）是一种新发现的天然类黄酮，存在于柑橘属植物和橄榄叶中，已被报道作为膳食补充剂可抑制癌症的进展。本研究旨在探讨 DSM 抑制肝癌（HCC）的特性及其可能的分子机制。选择 Hep3B 和 HCCLM3 细胞来评估 DSM 对 HCC 的抑制作用。使用 RNA 测序（RNA-seq）鉴定可能的分子靶标和途径。气相色谱-质谱联用（GC-MS）用于评估 DSM 处理对 HCCLM3 细胞初级代谢物的影响。在裸鼠中进行肿瘤异种移植实验以检验 DSM 的抗 HCC 特性。结果表明，DSM 呈剂量依赖性抑制 HCC 细胞的增殖和迁移。RNA-seq 鉴定出 4459 个差异表达基因（DEGs），这些基因在细胞周期途径中高度富集。此外，DSM 通过降低 BCL2、CDK1 和 CCND1 的表达，将细胞周期阻滞在 G1 期，从而调节细胞生长。此外，代谢组学分析表明，DSM 通过显著抑制代谢物（如乙酸、癸酸、甘油和 L-脯氨酸）的合成来干扰 HCC 细胞的脂质代谢途径。皮下肿瘤形成实验表明，与对照组相比，DSM 显著降低了肿瘤体积和重量。免疫组化分析进一步表明，DSM 处理显著降低了增殖标志物 KI67 的表达。我们的研究结果表明，DSM 通过抑制细胞增殖、细胞周期阻滞和干扰脂质代谢来发挥对 HCC 细胞的抗肿瘤作用。
