Neferine inhibits proliferation and migration of human prostate cancer stem cells through p38 MAPK/JNK activation.,Journal of Food Biochemistry

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Neferine inhibits proliferation and migration of human prostate cancer stem cells through p38 MAPK/JNK activation.
Journal of Food Biochemistry ( IF 3.5 ) Pub Date : 2020-05-11 , DOI: 10.1111/jfbc.13253
Suat Erdogan ₁ , Kader Turkekul ₁

Affiliation

Cancer stem cells (CSCs) are one of the significant causes of cancer treatment failure and metastasis, as they have significant chemo‐and radio‐resistance leading to tumor recurrence. Here we investigated the possible anticancer properties of neferine, a natural alkaloid, on human prostate cancer (PCa) cells and their stem cells. CD44⁺ CSCs were isolated from androgen‐insensitive PC3 cells by magnetic‐activated cell sorting system (MACS). Neferine dose‐and time‐dependently inhibited the viability of PC3 and CSCs as well as androgen‐sensitive LNCaP cells through inducing apoptosis and cell cycle arrest at G1 phase. Neferine was shown to downregulate the expression of Bcl‐2 and CDK4, and upregulate caspase 3, clePARP, p21, p27, and p53. The treatment significantly inhibits the migration of CSCs. Neferine induces JNK and p38 MAPK phosphorylation, and downregulates PI3K and NF‐ĸβ signaling. In conclusion, neferine may have a therapeutic effect inhibiting the PCa cell proliferation as well as by eliminating CSCs.

中文翻译：

Neferine通过p38 MAPK / JNK激活抑制人前列腺癌干细胞的增殖和迁移。

癌症干细胞（CSC）是导致癌症治疗失败和转移的重要原因之一，因为它们具有显着的化学和放射抗性，导致肿瘤复发。在这里，我们研究了天然生物碱奈费林对人前列腺癌（PCa）细胞及其干细胞的可能抗癌特性。CD44 ⁺通过磁激活细胞分选系统（MACS）从雄激素不敏感的PC3细胞中分离出CSC。肾上腺素通过诱导凋亡和细胞周期停滞在G1期，从而剂量和时间依赖性地抑制PC3和CSCs以及对雄激素敏感的LNCaP细胞的活力。证明Neferine下调Bcl-2和CDK4的表达，并上调caspase 3，clePARP，p21，p27和p53。该处理显着抑制了CSC的迁移。Neferine诱导JNK和p38 MAPK磷酸化，并下调PI3K和NF-β信号传导。总之，neferine可能具有抑制PCa细胞增殖以及消除CSC的治疗作用。

更新日期：2020-05-11

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