Integrated synchrotron radiation-based fourier transform infrared (SR-FTIR) microscopy and tandem-mass spectrometry (LC-MS/MS) used to elucidate the apoptotic effect of chamuangone in A549 cells

Abstract

Chamuangone, a natural compound extracted from Garcinia cowa leaves, has demonstrated potential in cancer therapeutics, but its effects on lung cancer cells remain unclear. This study investigates the apoptotic effects of Chamuangone on human lung adenocarcinoma cells (A549). The A549 cells were treated with Chamuangone, and the cytotoxic effects were evaluated using an MTT assay, revealing a dose-dependent inhibition of cell proliferation with an IC₅₀ value of 19.43 μM. Annexin V assays further confirmed that Chamuangone induces apoptosis in A549 cells, showing increased levels of late apoptosis with higher concentrations. Synchrotron radiation-based Fourier transform infrared (SR-FTIR) microscopy provided insights into macromolecular changes, highlighting significant alterations in proteins, lipids, and nucleic acids. These structural changes in key cellular macromolecules were supported by proteomic analysis, which identified the upregulation of apoptosis-related proteins, including Peroxiredoxin-2 and Na⁺/H⁺ exchange regulatory cofactor NHE-RF1. Canonical pathway analysis indicated that Chamuangone affects oxidative phosphorylation and mitochondrial dysfunction, both crucial pathways for apoptosis. Additionally, upstream regulator analysis demonstrated significant inhibition of the epidermal growth factor receptor (EGFR), a key player in lung cancer progression. These findings suggest that Chamuangone triggers apoptosis through mitochondrial pathways and EGFR inhibition, positioning it as a promising therapeutic candidate for lung cancer treatment.