Department of College of Tea and Food Science and Technology, Jiangsu Vocational College of Agriculture and Forestry, Zhenjiang, China.
School of Food and Biological Engineering, Jiangsu University, Zhenjiang, China.
J Food Biochem. 2021 May;45(5):e13683. doi: 10.1111/jfbc.13683. Epub 2021 Apr 12.
Liver cancer is one of the leading causes of cancer-related deaths in the world. Bitter melon seed (BMS) is well known for anti-inflammatory and anticancer properties. MicroRNA-421 (miR-421) is considered as a regulator of cancer initiation, tumor metastasis, and progression, interfering with transcription of the mRNAs responsible for the cancer pathogenesis. HepG2 cells were treated with BMS water extract (BMSW) for 24 hr, and the IC was 586.27 ± 0.07 µg/ml. The ROS, mitochondrial membrane potential, the protein expression, and the nuclear fragmentation after the treatment of BMSW were respectively detected. The increase of ROS resulted in the decrease of mitochondrial membrane potential, which induced the apoptosis of cells subsequently. BMSW inhibited the proliferation of HepG2 cells by blocking cell cycle in the S phase and influenced the nuclei and the expression of protein, leading to cellular laxity and apoptosis. The expression level of miR-421 in HepG2 was distinctly down-regulated by 13.74 fold with 600 µg/ml of BMSW. Comprehensive microarray and RT-PCR analysis identified six putative target genes of miR-421 (GADD45B, DUSP6, DUSP3, DUSP10, CASP3, and CAPN2). The relationships of DUSP6, CASP3, and miR-421 were further confirmed by miR-421 mimics/inhibitor transfection by RT-PCR and western blot. The CASP3 was identified as target gene of miR-421. BMSW induced the apoptosis of HepG2 cell by regulating miR-421 and CASP3. PRACTICAL APPLICATIONS: Hepatocellular carcinoma (HCC) is a malignant tumour with the fourth highest mortality rate in the world. Bitter melon seed (BMS) as edible and medical food has significant anticancer activity. Our study indicated the anticancer mechanisms of BMS and provided the scientific basis for the application of BMS in healthy or novel functional foods. BMS can be used as dietary supplements or nutritional fortifiers to improve the survival status of patients with liver cancer due to safety and effectiveness.
肝癌是全球癌症相关死亡的主要原因之一。苦瓜籽 (Bitter melon seed, BMS) 以其抗炎和抗癌特性而闻名。microRNA-421 (miR-421) 被认为是癌症起始、肿瘤转移和进展的调节剂，干扰负责癌症发病机制的 mRNA 的转录。将 HepG2 细胞用 BMS 水提取物 (BMSW) 处理 24 小时，IC 为 586.27±0.07 µg/ml。分别检测 BMSW 处理后的 ROS、线粒体膜电位、蛋白表达和核片段化。ROS 的增加导致线粒体膜电位降低，随后诱导细胞凋亡。BMSW 通过阻断 S 期细胞周期抑制 HepG2 细胞增殖，并影响核和蛋白表达，导致细胞松弛和凋亡。用 600 µg/ml 的 BMSW 将 HepG2 中的 miR-421 的表达水平明显下调 13.74 倍。综合微阵列和 RT-PCR 分析鉴定出 miR-421 的六个可能靶基因（GADD45B、DUSP6、DUSP3、DUSP10、CASP3 和 CAPN2）。通过 RT-PCR 和 Western blot 进一步证实了 miR-421 模拟物/抑制剂转染后 DUSP6、CASP3 和 miR-421 之间的关系。CASP3 被鉴定为 miR-421 的靶基因。BMSW 通过调节 miR-421 和 CASP3 诱导 HepG2 细胞凋亡。实际应用：肝细胞癌 (HCC) 是世界上死亡率第四高的恶性肿瘤。苦瓜籽 (Bitter melon seed, BMS) 作为食用和药用食品，具有显著的抗癌活性。我们的研究表明了 BMS 的抗癌机制，并为 BMS 在健康或新型功能性食品中的应用提供了科学依据。由于安全性和有效性，BMS 可用作膳食补充剂或营养强化剂，以改善肝癌患者的生存状况。
