Department of Zoology, West Bengal State University, Berunanpukuria, Malikapur, North-24 Parganas, Barasat, Kolkata-700126, West Bengal, India.
Department of Life Science and Bioinformatics, Assam University, Silchar-788011, India.
Food Funct. 2020 Oct 21;11(10):9020-9034. doi: 10.1039/d0fo00887g.
The transforming growth factor-β (TGF-β) signaling is considered to be a key player in gastric cancer metastasis, and the inhibition of the TGF-β/SMAD4 signaling pathway may be a novel strategy for therapeutic interventions in cancer. Here, the anti-metastatic activity of two phytochemicals, eugenol and capsaicin, has been studied, and their potential to antagonize TGF-β has been investigated in gastric cancer cells. Both the phytochemicals exhibited anti-metastatic activity by inhibiting the TGF-β signaling pathway independent of P21 or P53, with capsaicin proving to be more potent than eugenol. However, unlike eugenol, the inhibitory effect of capsaicin on the TGF-β signaling pathway and metastasis was found to be dependent on SMAD4, which was validated in SMAD4-knocked down AGS cell and SMAD4-null SW620 cell line. Furthermore, the use of recombinant TGF-β and TGF-β receptor inhibitor LY2109761 confirmed that the anti-metastatic activity of eugenol is partially and that of capsaicin is principally mediated through the TGF-β signaling pathway. Identifying phytochemicals with the potential to inhibit cancer metastasis by targeting the TGF-β signaling pathway has immense scope for developing a therapeutic strategy against cancer metastasis.
转化生长因子-β（TGF-β）信号被认为是胃癌转移的关键因素，抑制 TGF-β/SMAD4 信号通路可能是癌症治疗干预的一种新策略。在这里，研究了两种植物化学物质，丁香酚和辣椒素，它们在胃癌细胞中拮抗 TGF-β 的潜力及其抗转移活性。这两种植物化学物质都通过独立于 P21 或 P53 的 TGF-β 信号通路抑制来表现出抗转移活性，其中辣椒素比丁香酚更有效。然而，与丁香酚不同，辣椒素对 TGF-β 信号通路和转移的抑制作用被发现依赖于 SMAD4，这在 SMAD4 敲低的 AGS 细胞和 SMAD4 缺失的 SW620 细胞系中得到了验证。此外，使用重组 TGF-β 和 TGF-β 受体抑制剂 LY2109761 证实，丁香酚的抗转移活性部分，而辣椒素的抗转移活性主要通过 TGF-β 信号通路介导。通过靶向 TGF-β 信号通路，确定具有抑制癌症转移潜力的植物化学物质，为开发针对癌症转移的治疗策略提供了广阔的前景。
