Natural alkaloids as potential treatments for esophageal squamous-cell carcinoma: A comprehensive review

Esophageal squamous cell carcinoma (ESCC) is the most dangerous variant of esophageal cancer, and the most common in developing countries. Its ever-increasing incidence, due to cell resistance to available drugs and side effects, is prompting the scientific community to find new solutions. Alternatively, alkaloids are a large group of secondary metabolites found in plants and characterized by the presence of at least one nitrogen group in their structure. Thus, the aim of the research of is to thoroughly examine alkaloids that may offer an alternate course of treatment for esophageal squamous cell carcinoma. To achieve this, literature searches were conducted in databases such as Web of Science, PubMed/Medline, and Scopus to identify articles that explored the effect of alkaloids on esophageal squamous cell carcinoma as a primary or secondary objective. This methodology enabled us to obtain 7 studies and 6 alkaloids (neferine, matrine, tetrandine, d-dicentrine, synephrine, and 8-(4-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydro-2-methylquin-oline or (83b1)). d-dicentrine (0.40 ​μM ​< ​IC50 ​< ​4.932 ​μM), and Matrine (1.50 ​mg/mL ​< ​IC50 ​< ​1.94 ​mg/mL) have significant activities on ESCC. They act by arresting cell cycle at the G2/M and G1/G0 phases respectively. Tetrandrine produces a synergistic effect when combined with cisplatin (IC₅₀ ​= ​4.57 ​μg/mL) and reverses the resistance of cisplatin-resistant ESCC cells by inhibiting MRP1. The others molecules have a moderate anti-ESCC effect. In conclusion, d-dicentrine, matrine and tetrandrine represent an important therapeutic avenue in the fight against esophageal squamous cell carcinoma. However, future research should focus on determining the toxicological potential of d-dicentrine.