Methoxylated Cinnamic Esters with Antiproliferative and Antimetastatic Effects on Human Lung Adenocarcinoma Cells

• Published in: Life (Basel, Switzerland) Vol. 13; no. 7; p. 1428
• Main Authors: Sampaio, João Graciano, Pressete, Carolina Girotto, Costa, Adilson Vidal, Martins, Felipe Terra, de Almeida Lima, Graziela Domingues, Ionta, Marisa, Teixeira, Róbson Ricardo
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22.06.2023; MDPI
• Subjects: Acids; Adenocarcinoma; Alcohol; Annexin V; Antimitotic agents; Antineoplastic agents; antiproliferative activity; Antiproliferatives; Antitumor agents; Apoptosis; Assaying; Cancer therapies; Cell cycle; Cell viability; Chromatography; Cinnamic acid; Cyclin B; Drug development; Drug therapy; Drugs; Esters; Extracellular signal-regulated kinase; Health aspects; Kinases; Lung cancer; Lung cancer, Non-small cell; MAP kinase; Melanoma; Metastases; monomethoxylated cinnamic acid derivatives; NMR; Non-small cell lung carcinoma; non-small-cell lung cancer; Nuclear magnetic resonance; Organic acids; Pharmaceutical research; Signal transduction; Skin cancer; Sodium; Temperature; Western blotting; Wound healing; Brazil; Palo Alto California; United States > US; Japan; antiproliferative activity; monomethoxylated cinnamic acid derivatives; non-small-cell lung cancer
• ISSN: 2075-1729; 2075-1729
• 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.