College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China.
College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China.
Phytochemistry. 2022 Aug;200:113217. doi: 10.1016/j.phytochem.2022.113217. Epub 2022 Apr 30.
Berberine alkaloids belong to the class of isoquinoline alkaloids that have been shown to possess anticancer potential, berberine exhibits inhibitory effects on breast cancer development. However, the exact mechanisms of action for anti-breast carcinoma of the alkaloids, including epiberberine, berberrubine and dihydroberberine are still unclear. MTT assay, colony formation, wound healing and transwell invasion assays detected these alkaloids suppressed proliferation, migration and invasion of breast cancer cells. Hoechst and Annexin V-FITC/PI staining were used to analyze the apoptosis of breast cancer cells. Western blotting investigated the changes noted in the expression levels of the key proteins involved in the Wnt/β-catenin signaling pathway and epithelial to mesenchymal transition (EMT). The results showed that inhibited the proliferation of breast cancer cells. Berberine alkaloids inhibited the cell cycle at G2/M phase in MCF-7 cells, but in MDA-MB-231 cells berberine alkaloids arrested the cell cycle in G0/G1 and G2/M phases. By decreasing β-catenin expression, increasing GSK-3β expression and decreasing N-cadherin expression, increasing E-cadherin expression, which proved that epiberberine, berberrubine and dihydroberberine inhibited of metastasis of breast cancer cells through Wnt signaling pathway and reversed EMT except berberine. Furthermore, berberine alkaloids exert their anti-breast cancer effects through the synergistic action of intrinsic and extrinsic pathways of apoptosis. These findings highlight the different effects of different berberine alkaloids on breast cancer cells and confirm that berberine alkaloids may be potentially used in the treatment of breast cancer.
小檗碱生物碱属于异喹啉生物碱类，已被证明具有抗癌潜力，小檗碱对乳腺癌的发展具有抑制作用。然而，包括表小檗碱、小檗红碱和二氢小檗碱在内的生物碱抗乳腺癌的确切作用机制仍不清楚。MTT 检测、集落形成、划痕愈合和 Transwell 侵袭实验检测到这些生物碱抑制乳腺癌细胞的增殖、迁移和侵袭。Hoechst 和 Annexin V-FITC/PI 染色分析乳腺癌细胞的凋亡。Western blot 检测参与 Wnt/β-catenin 信号通路和上皮间质转化（EMT）的关键蛋白表达水平的变化。结果表明，小檗碱生物碱抑制乳腺癌细胞的增殖。小檗碱生物碱在 MCF-7 细胞中使细胞周期停滞在 G2/M 期，但在 MDA-MB-231 细胞中，小檗碱生物碱使细胞周期停滞在 G0/G1 和 G2/M 期。通过降低β-catenin 表达，增加 GSK-3β 表达和降低 N-钙粘蛋白表达，增加 E-钙粘蛋白表达，证明表小檗碱、小檗红碱和二氢小檗碱通过 Wnt 信号通路抑制乳腺癌细胞的转移，并逆转 EMT，除了小檗碱。此外，小檗碱生物碱通过凋亡的内在和外在途径的协同作用发挥其抗乳腺癌作用。这些发现强调了不同的小檗碱生物碱对乳腺癌细胞的不同影响，并证实小檗碱生物碱可能在乳腺癌的治疗中具有潜在的应用价值。
