Department of Surgery, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
J Cancer Res Clin Oncol. 2013 Apr;139(4):563-72. doi: 10.1007/s00432-012-1352-6. Epub 2012 Nov 16.
Curcumin has been shown to have potent anticancer activities like inhibition of cell proliferation, induction of apoptosis, and suppression of angiogenesis. Transforming growth factor-β (TGF-β) signaling plays a complex role in tumor suppression and promotion depending on the tumor type and stage. However, the effect of curcumin on TGF-β signaling in cancer cells and the role of TGF-β signaling in curcumin-induced anticancer activities have not been determined. Here, we investigate the role of curcumin on TGF-β signaling, and whether TGF-β signaling is involved in the antitumor activities of curcumin.
Human non-small cell lung cancer (NSCLC) cell lines, ACC-LC-176 (without TGF-β signaling), H358, and A549 (with TGF-β signaling) were treated with curcumin to determine cell growth, apoptosis, and tumorigenicity. Antitumor activities of curcumin were determined using these cell lines and an in vivo mouse model. We also tested the effect of curcumin on TGF-β/Smad signaling by western blotting and by luciferase assays.
Curcumin inhibited cell growth and induced apoptosis of all three NSCLC cell lines in vitro and in vivo. It significantly reduced subcutaneous tumor growth by these three cell lines irrespective of TGF-β signaling status. Curcumin inhibited TGF-β-induced Smad2/3 phosphorylation and transcription in H358 and A549 cells, but not in ACC-LC-176 cells.
Curcumin reduces tumorigenicity of human lung cancer cells in vitro and in vivo by inhibiting cell proliferation and promoting apoptosis. These results suggest that TGF-β signaling is not directly involved in curcumin-mediated growth inhibition, induction of apoptosis, and inhibition of tumorigenicity.
姜黄素具有抑制细胞增殖、诱导细胞凋亡和抑制血管生成等强大的抗癌活性。转化生长因子-β（TGF-β）信号转导在肿瘤抑制和促进方面发挥着复杂的作用，这取决于肿瘤的类型和阶段。然而，姜黄素对癌细胞中 TGF-β 信号转导的影响以及 TGF-β 信号转导在姜黄素诱导的抗癌活性中的作用尚未确定。在这里，我们研究了姜黄素对 TGF-β 信号转导的作用，以及 TGF-β 信号转导是否参与姜黄素的抗肿瘤活性。
用姜黄素处理人非小细胞肺癌（NSCLC）细胞系 ACC-LC-176（无 TGF-β 信号转导）、H358 和 A549（有 TGF-β 信号转导），以确定细胞生长、凋亡和致瘤性。使用这些细胞系和体内小鼠模型来确定姜黄素的抗肿瘤活性。我们还通过 Western blot 和荧光素酶报告基因分析检测了姜黄素对 TGF-β/Smad 信号转导的影响。
姜黄素在体外和体内抑制了三种 NSCLC 细胞系的细胞生长并诱导了细胞凋亡。它显著降低了这三种细胞系的皮下肿瘤生长，而与 TGF-β 信号转导状态无关。姜黄素抑制了 H358 和 A549 细胞中 TGF-β 诱导的 Smad2/3 磷酸化和转录，但不抑制 ACC-LC-176 细胞。
姜黄素通过抑制细胞增殖和促进细胞凋亡来降低人肺癌细胞在体外和体内的致瘤性。这些结果表明，TGF-β 信号转导不直接参与姜黄素介导的生长抑制、细胞凋亡诱导和肿瘤抑制作用。
