据报道，柑橘八萨克提取物可激活 AMPK。由于该提取物含有丰富的 aurapten，我们研究了纯 aurapten 是否可以激活 AMPK 并抑制前列腺癌细胞系的增殖。事实上，aurapten 抑制 LNCaP 细胞的增殖和迁移，并诱导 LNCaP、PC3 和 HEK-293 细胞中 AMPK 或其下游 ACC 的磷酸化，但在不表达 LKB1 的 DU145 细胞中则不然。此外，位于激活的 AMPK 下游的 mTOR-S6K 通路也被 auraaptene 治疗显着抑制。重要的是，研究表明，auaptene 可在蛋白质和 mRNA 水平上降低雄激素受体 (AR) 和前列腺特异性抗原 (PSA) 的表达。这种auaptene诱导的PSA下调可通过AMPK siRNA或AMPK抑制剂化合物C的治疗部分但显着地逆转，表明AMPK激活至少部分是起因。最后，在缺乏 LKB1 基因的 DU145 细胞中，外源诱导的 LKB1 表达恢复了 aauaptene 的 AMPK 磷酸化，表明了 LKB1 的重要作用。总之，auaptene 是一种有效的 AMPK 激活剂，通过提高 AMP/ATP 比率发挥作用，从而可能通过至少三种分子机制抑制前列腺癌的进展，包括抑制 mTOR-S6K 通路、减少脂质合成和引起的 AR 下调通过 AMPK 激活。

Citrus hassaku extract reportedly activates AMPK. Because this extract contains an abundance of auraptene, we investigated whether pure auraptene activates AMPK and inhibits proliferation using prostate cancer cell lines. Indeed, auraptene inhibited the proliferation and migration of LNCaP cells and induced phosphorylation of AMPK or its downstream ACC in LNCaP, PC3, and HEK-293 cells, but not in DU145 cells not expressing LKB1. In addition, the mTOR-S6K pathway, located downstream from activated AMPK, was also markedly suppressed by auraptene treatment. Importantly, it was shown that auraptene reduced androgen receptor (AR) and prostate-specific antigen (PSA) expressions at both the protein and the mRNA level. This auraptene-induced downregulation of PSA was partially but significantly reversed by treatment with AMPK siRNA or the AMPK inhibitor compound C, suggesting AMPK activation to, at least partially, be causative. Finally, in DU145 cells lacking the LKB1 gene, exogenously induced LKB1 expression restored AMPK phosphorylation by auraptene, indicating the essential role of LKB1. In summary, auraptene is a potent AMPK activator that acts by elevating the AMP/ATP ratio, thereby potentially suppressing prostate cancer progression, via at least three molecular mechanisms, including suppression of the mTOR-S6K pathway, reduced lipid synthesis, and AR downregulation caused by AMPK activation.