School of Biomolecular and Biomedical Sciences, Conway Institute, University College Dublin, Dublin, Ireland.
Systems Biology Ireland, School of Medicine, University College Dublin, Belfield, Dublin, Ireland.
Molecules. 2021 Oct 18;26(20):6302. doi: 10.3390/molecules26206302.
The natural compound curcumin has been shown to have therapeutic potential against a wide range of diseases such as cancer. Curcumin reduces cell viability of renal cell carcinoma (RCC) cells when combined with TNF-related apoptosis-inducing ligand (TRAIL), a cytokine that specifically targets cancer cells, by helping overcome TRAIL resistance. However, the therapeutic effects of curcumin are limited by its low bioavailability. Similar compounds to curcumin with higher bioavailability, such as demethoxycurcumin (DMC) and 3,5-bis(2-fluorobenzylidene)-4-piperidone (EF24), can potentially have similar anticancer effects and show a similar synergy with TRAIL, thus reducing RCC viability. This study aims to show the effects of DMC and EF24 in combination with TRAIL at reducing ACHN cell viability and ACHN cell migration. It also shows the changes in death receptor 4 (DR4) expression after treatment with these compounds individually and in combination with TRAIL, which can play a role in their mechanism of action.
天然化合物姜黄素已被证明具有治疗多种疾病的潜力，如癌症。姜黄素与肿瘤坏死因子相关凋亡诱导配体（TRAIL）联合使用时，通过帮助克服 TRAIL 耐药性，降低肾细胞癌（RCC）细胞的细胞活力，TRAIL 是一种专门针对癌细胞的细胞因子。然而，姜黄素的治疗效果受到其低生物利用度的限制。具有更高生物利用度的类似姜黄素的化合物，如去甲氧基姜黄素（DMC）和 3,5-双（2-氟苯亚甲基）-4-哌啶酮（EF24），可能具有类似的抗癌作用，并与 TRAIL 显示出类似的协同作用，从而降低 RCC 的活力。本研究旨在显示 DMC 和 EF24 与 TRAIL 联合使用在降低 ACHN 细胞活力和 ACHN 细胞迁移中的作用。它还显示了这些化合物单独和与 TRAIL 联合使用后死亡受体 4（DR4）表达的变化，这可能在其作用机制中发挥作用。
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