Molecular Oncology and Viral Pathology GRP-IC, Portuguese Institute of Oncology of Porto (IPO Porto), Rua António Bernardino de Almeida, 4200-072 Porto, Portugal.
ICBAS-School of Medicine and Biomedical Sciences, Port University, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
Molecules. 2023 Feb 25;28(5):2159. doi: 10.3390/molecules28052159.
Chalcones are synthetic and naturally occurring compounds that have been widely investigated as anticancer agents. In this work, the effect of chalcones - against the metabolic viability of cervical (HeLa) and prostate (PC-3 and LNCaP) tumor cell lines was tested, to compare the activity against solid and liquid tumor cells. Their effect was also evaluated on the Jurkat cell line. Chalcone showed the highest inhibitory effect on the metabolic viability of the tested tumor cells and was selected for further studies. Recent antitumor therapies include compounds with the ability to influence immune cells on the tumor microenvironment, with immunotherapy being one actual goal in cancer treatment. Therefore, the effect of chalcone on the expression of mTOR, HIF-1α, IL-1β, TNF-α, IL-10, and TGF-β, after THP-1 macrophage stimulation (none, LPS or IL-4), was evaluated. Chalcone significantly increased the expression of mTORC1, IL-1β, TNF-α, and IL-10 of IL-4 stimulated macrophages (that induces an M2 phenotype). HIF-1α and TGF-β were not significantly affected. Chalcone also decreased nitric oxide production by the RAW 264.7 murine macrophage cell line, this effect probably being due to an inhibition of iNOS expression. These results suggest that chalcone may influence macrophage polarization, inducing the pro-tumoral M2 macrophages (IL-4 stimulated) to adopt a profile closer to the antitumor M1 profile.
查耳酮是一种合成的天然化合物，已被广泛研究作为抗癌剂。在这项工作中，测试了查耳酮对宫颈（HeLa）和前列腺（PC-3 和 LNCaP）肿瘤细胞系代谢活力的影响，以比较对实体瘤和液体肿瘤细胞的活性。还评估了它们对 Jurkat 细胞系的作用。查耳酮 对测试的肿瘤细胞代谢活力具有最高的抑制作用，因此被选为进一步研究的对象。最近的抗肿瘤治疗包括具有影响肿瘤微环境中免疫细胞能力的化合物，免疫疗法是癌症治疗的一个实际目标。因此，评估了查耳酮 对 THP-1 巨噬细胞刺激（无、LPS 或 IL-4）后 mTOR、HIF-1α、IL-1β、TNF-α、IL-10 和 TGF-β 表达的影响。查耳酮 显著增加了 IL-4 刺激的巨噬细胞中 mTORC1、IL-1β、TNF-α 和 IL-10 的表达（诱导 M2 表型）。HIF-1α 和 TGF-β 没有明显影响。查耳酮 还降低了 RAW 264.7 鼠巨噬细胞系的一氧化氮产生，这种作用可能是由于抑制了 iNOS 表达。这些结果表明，查耳酮 可能影响巨噬细胞极化，诱导促肿瘤 M2 巨噬细胞（IL-4 刺激）采用更接近抗肿瘤 M1 表型的特征。
