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多酚类化合物α-松柏苷通过作用于多种信号分子发挥抗结肠癌和抗血管生成作用。

The polyphenolic compound, α-conidendrin, exerts anti-colon cancer and anti-angiogenic effects by targeting several signaling molecules.

作者信息

Mottaghi Sayeh, Abbaszadeh Hassan, Valizadeh Armita, Hafezi Katayoon

机构信息

Department of Pediatrics, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Department of Pharmacology, Faculty of Pharmacy, Medicinal Plants Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr 10. doi: 10.1007/s00210-025-04090-2.

Abstract

Our previous study indicated that α-conidendrin had considerable anti-proliferative activities against breast cancer cell lines. The present study aimed to evaluate the anti-colon cancer and anti-angiogenic influences of α-conidendrin as well as its molecular mechanisms. The findings of the current study demonstrate that α-conidendrin possesses potent anti-colon cancer and anti-angiogenic effects. α-Conidendrin significantly inhibited the proliferation of colon cancer cells. This polyphenolic compound induced caspase-mediated apoptosis in HT-29 cells by modulating the PTEN/PI3K/Akt/mTOR signaling pathway. α-Conidendrin markedly upregulated the protein expression of PTEN and downregulated the protein expression of p-PI3K, p-AKt, and p-mTOR. The protein expression of caspase-3 and caspase-9 enhanced in colon cancer cells following treatment with α-conidendrin. This study also revealed the anti-angiogenic activities of α-conidendrin in the ex vivo and in vitro models. α-Conidendrin significantly downregulated the mRNA expression of HIF-1α, VEGF, MMP-2, and MMP-9 in endothelial cells. These data highlight that α-conidendrin can act as a novel and promising anti-cancer and anti-angiogenic agent for treatment of colon cancer.

摘要

我们之前的研究表明,α-松柏苷对乳腺癌细胞系具有显著的抗增殖活性。本研究旨在评估α-松柏苷的抗结肠癌和抗血管生成作用及其分子机制。当前研究结果表明,α-松柏苷具有强大的抗结肠癌和抗血管生成作用。α-松柏苷显著抑制结肠癌细胞的增殖。这种多酚化合物通过调节PTEN/PI3K/Akt/mTOR信号通路诱导HT-29细胞中caspase介导的凋亡。α-松柏苷显著上调PTEN的蛋白表达,下调p-PI3K、p-AKt和p-mTOR的蛋白表达。用α-松柏苷处理后,结肠癌细胞中caspase-3和caspase-9的蛋白表达增强。本研究还揭示了α-松柏苷在体内外模型中的抗血管生成活性。α-松柏苷显著下调内皮细胞中HIF-1α、VEGF、MMP-2和MMP-9的mRNA表达。这些数据表明,α-松柏苷可作为一种新型且有前景的抗癌和抗血管生成药物用于结肠癌的治疗。

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