Antiproliferative Activity of α-Tomatine and Molecular Target Identification

α-tomatine is a glycoalkaloid derived from tomato varietiesthat has been reported to possess various anticancer properties. However, its inhibitory effects on epidermal growth factor receptorisstill poorly understood. The aim of this study is to investigate the anticancer effect of α-tomatine and its related mechanisms in lung cancer cells.Cytotoxicity and apoptosis induction of α-tomatine were determined by MTT assay and annexin V-FITC staining methods, respectively.For tyrosine kinase activity, TK-1 kinase selectivity profiling assay and molecular modelling study were performed. The DNA cleavage activityof α-tomatinewas investigated using agarose gel electrophoretic method. α-tomatine proved to possess an outstanding antiproliferative activity against A549 and Jurkat cells without noticeable toxicity on PBMC. The results indicated that α-tomatinehas a significant inhibition effect on both EGFR and HER2. α-tomatineformed some key interaction into ATP binding sites of EGFR and HER2. Furthermore, α-tomatine strongly disintegrated DNA atlowconcentrations in the presence of iron(II) complexes. The current findings suggest that α-tomatine has a distinguished receptor tyrosine kinase inhibition profile from erlotinib and might be a potential drug candidate for treatment of NSCLC.

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