Screening, validation, and mechanism study of antitumor components from Dioscorea nipponica Makino subsp. rosthornii based on spectrum-effect relationship analysis

Objectives This study aimed to screen potential antitumor compounds from Dioscorea nipponica Makino subsp. rosthornii , validate them in cellular models, and investigate their mechanisms underlying the inhibition of proliferation in A549 cells. Methods The chemical constituents in 12 batches of D. nipponica Makino subsp. rosthornii were identified using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). The antitumor activity of these samples was assessed in A549 cells through cell proliferation, wound healing, migration, and invasion assays. A multivariate regression spectrum-effect relationship model was developed, treating the peak areas of common chromatographic peaks as independent variables and the antitumor activity as the dependent variable. Potential antitumor components were identified based on this spectrum-effect correlation and subsequently validated. The protein expression levels of N-cadherin, MMP2, and E-cadherin in A549 cells were measured to investigate the underlying mechanisms. Results A comprehensive chemical analysis was conducted on 12 batches of D. nipponica Makino subsp. rosthornii from varied geographical origins using UPLC-QTOF-MS, resulting in the identification of 23 distinct chemical constituents. The extract derived from D. nipponica Makino subsp. rosthornii notably inhibited the proliferation, migration, and invasion of A549 cells. Spectrum-effect relationship analysis pinpointed three potential antitumor compounds: protodioscin, diosgenin, and gracillin. Further mechanistic investigations demonstrated that these saponins inhibit the malignant phenotype of A549 cells through a dual regulatory mechanism. Specifically, they markedly reduced the expression of pro-metastatic proteins N-cadherin and MMP2, while simultaneously enhancing the expression of E-cadherin. Conclusion This study elucidated the key active constituents responsible for the antitumor effects of D . nipponica Makino subsp. rosthornii , thereby providing scientific evidence to support its potential application in cancer therapy.