College of Food Science , Shenyang Agricultural University , 120 Dongling Road , Shenhe District, Shenyang , Liaoning 100866 , People's Republic of China.
J Agric Food Chem. 2019 Jan 16;67(2):625-636. doi: 10.1021/acs.jafc.8b06209. Epub 2019 Jan 7.
Anthocyanin, a natural antioxidant, is reported to have cytotoxicity against cancer cells; however, the mechanism remains unclear. The aim of the present study was to investigate the mechanism by which malvidin-3-galactoside (M3G), the prominent anthocyanin in blueberry, suppresses the development of hepatocellular carcinoma. In vitro, M3G suppressed the proliferation, polarization, migration, and invasion activities of HepG2 cells by regulating the protein expression of cyclin D1, cyclin B, cyclin E, caspase-3, cleaved caspase-3, Bax, p-JNK, and p-p38, activating phosphatase and tensin homologue deleted on chromosome 10 (PTEN), accompanied by a decrease in the p-AKT level, and lowering the protein expression levels of MMP-2 and MMP-9. In vivo, M3G promoted the apoptosis of liver tumor cells, as determined by immunohistochemistry (cleaved caspase-3, Ki-67, PTEN, and p-AKT), a terminal deoxynucleotidyl transferase dUTP nick end labeling assay, and hematoxylin-eosin staining. Overall, these results suggest that M3G, as an adjuvant ingredient or nutritional supplement, may be beneficial for liver cancer prevention and the modulatory mechanism seems to be associated with inhibition of proliferation, apoptosis, migration, and invasion-related pathways.
花色苷是一种天然抗氧化剂，据报道对癌细胞具有细胞毒性，但作用机制尚不清楚。本研究旨在探讨矢车菊素-3-半乳糖苷（M3G）抑制肝癌发展的机制，M3G 是蓝莓中主要的花色苷。在体外，M3G 通过调节细胞周期蛋白 D1、细胞周期蛋白 B、细胞周期蛋白 E、半胱天冬酶-3、裂解半胱天冬酶-3、Bax、p-JNK 和 p-p38 的蛋白表达，激活磷酸酶和张力蛋白同源物缺失的 10 号染色体（PTEN），同时降低 p-AKT 水平，降低 MMP-2 和 MMP-9 的蛋白表达水平，抑制 HepG2 细胞的增殖、极化、迁移和侵袭活性。在体内，通过免疫组织化学（裂解半胱天冬酶-3、Ki-67、PTEN 和 p-AKT）、末端脱氧核苷酸转移酶 dUTP 缺口末端标记测定和苏木精-伊红染色，M3G 促进了肝肿瘤细胞的凋亡。总之，这些结果表明，M3G 作为辅助成分或营养补充剂，可能有益于肝癌的预防，其调节机制似乎与抑制增殖、凋亡、迁移和侵袭相关途径有关。
