loading page

Quantitative MALDI-MSI combined with LC-MS/MS metabolomics analysis to study the inhibition of solasonine in lung cancer
  • +4
  • chunzi Shi,
  • mingming jin,
  • shengjie lu,
  • xiyu liu,
  • junru wen,
  • xiaoyan he,
  • gang huang
chunzi Shi
Shanghai University of Traditional Chinese Medicine
Author Profile
mingming jin
Shanghai University of Traditional Chinese Medicine
Author Profile
shengjie lu
Shanghai University of Traditional Chinese Medicine
Author Profile
xiyu liu
Shanghai University of Traditional Chinese Medicine
Author Profile
junru wen
Shanghai University of Traditional Chinese Medicine
Author Profile
xiaoyan he
Shanghai University of Medicine and Health Sciences
Author Profile
gang huang
Shanghai University of Medicine and Health Sciences
Author Profile

Abstract

Background and purpose: The Chinese medicine monomer solasonine has been shown to be an effective inhibitor of Lung adenocarcinoma in vitro and in vivo. The research on the application of solasonine in lung cancer mostly involves the cell level, the lack of information on the spatial distribution of drugs and related metabolic pathways are common problems faced by many Chinese medicine monomers. Experimental Approach: LC-MS/MS metabolomics analysis was performed to reveal the underlying regulatory mechanism, matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and 3D computational reconstruction were applied to illustrated the spatial-temporal distribution of solasonine. Solamargine was chosen as the internal standard to correct the calibration curve due to the similarity in structure. Key Results: Metabolomics analysis illustrated that solasonine promotes A549 cells ferroptosis via GPX4-induced destruction of the glutathione redox system. Detailed distribution features of solasonine in different organs were revealed by MALDI-MSI after intravenous administration in the mice. The heterogeneity of solasonine distribution and penetration in tumor demonstrated that significant drug deposits around the necrotic area. Conclusion and Implication: The anti-tumor mechanism of solasonine associated with ferroptosis is identified for the first time. It provides an additional basis for the previous conclusion that solasonine promotes tumor necrosis. Quantitative spatial-temporal information obtained here can improve our understanding of pharmacokinetics (PK), pharmacodynamics (PD), potential transient toxicities of solasonine in organs, and possibly direct further optimization of drug properties to reduce drug-induced organ toxicity and broaden the scope of application.