Sampaio João Graciano, Pressete Carolina Girotto, Costa Adilson Vidal, Martins Felipe Terra, de Almeida Lima Graziela Domingues, Ionta Marisa, Teixeira Róbson Ricardo
Grupo de Síntese e Pesquisa de Compostos Bioativos (GSPCB), Departamento de Química, Universidade Federal de Viçosa, Viçosa 36570-900, MG, Brazil.
Programa de Pós-Graduação em Biociências Aplicadas à Saúde, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Alfenas 37130-000, MG, Brazil.
Life (Basel). 2023 Jun 22;13(7):1428. doi: 10.3390/life13071428.
Lung cancer is the leading cause of cancer mortality worldwide, and malignant melanomas are highly lethal owing to their elevated metastatic potential. Despite improvements in therapeutic approaches, cancer treatments are not completely effective. Thus, new drug candidates are continuously sought. We synthesized mono- and di-methoxylated cinnamic acid esters and investigated their antitumor potential. A cell viability assay was performed to identify promising substances against A549 (non-small-cell lung cancer) and SK-MEL-147 (melanoma) cells. ()-2,5-dimethoxybenzyl 3-(4-methoxyphenyl)acrylate (), a monomethoxylated cinnamic acid derivative, was identified as the lead antitumor compound, and its antitumor potential was deeply investigated. Various approaches were employed to investigate the antiproliferative (clonogenic assay and cell cycle analysis), proapoptotic (annexin V assay), and antimigratory (wound-healing and adhesion assays) activities of on A549 cells. In addition, western blotting was performed to explore its mechanism of action. We demonstrated that inhibits the proliferation of A549 by promoting cyclin B downregulation and cell cycle arrest at G2/M. Antimigratory and proapoptotic activities of on A549 were also observed. The antitumor potential of involved its ability to modulate the mitogen-activated protein kinases/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway once phosphorylated-ERK expression was considerably reduced in response to treatment. Our findings demonstrate that is a promising anticancer drug candidate.
肺癌是全球癌症死亡的主要原因，恶性黑色素瘤因其转移潜力高而具有高度致死性。尽管治疗方法有所改进，但癌症治疗并不完全有效。因此，人们不断寻找新的候选药物。我们合成了单甲氧基和二甲氧基肉桂酸酯，并研究了它们的抗肿瘤潜力。进行细胞活力测定以鉴定对A549（非小细胞肺癌）和SK-MEL-147（黑色素瘤）细胞有前景的物质。（）-2,5-二甲氧基苄基3-（4-甲氧基苯基）丙烯酸酯（），一种单甲氧基肉桂酸衍生物，被鉴定为主要抗肿瘤化合物，并对其抗肿瘤潜力进行了深入研究。采用多种方法研究了其对A549细胞的抗增殖（克隆形成测定和细胞周期分析）、促凋亡（膜联蛋白V测定）和抗迁移（伤口愈合和黏附测定）活性。此外，进行蛋白质印迹以探索其作用机制。我们证明，通过促进细胞周期蛋白B下调和使细胞周期停滞在G2/M期来抑制A549细胞的增殖。还观察到其对A549细胞的抗迁移和促凋亡活性。其抗肿瘤潜力涉及其一旦磷酸化的ERK表达因治疗而显著降低时调节丝裂原活化蛋白激酶/细胞外信号调节激酶（MAPK/ERK）信号通路的能力。我们的研究结果表明，是一种有前景的抗癌候选药物。
