Effect and Mechanism of Tanshinone I on the Radiosensitivity of Lung Cancer Cells

Background:
Resistance to radiotherapy is one of the main obstacles
to improving cancer prognoses. To effectively destroy cancer cells,
novel radiation sensitizers are needed. Recently, several natural
products have been shown to exhibit promising tumor-killing properties.
However, little is known about the specific mechanisms of these natural
compounds on cancer treatment. In this study, after screening a high-throughput
natural product library, we identified tanshinone I (Tan I) as a potential
radiation sensitizer in lung cancer cells. Methods: Lung cancer radioresistant
cell lines, H358-IR and H157-IR, were first established to confirm
the radioresistant phenotypes. After that, a natural product library
was used to screen the potential radiation sensitizer. We further
examined the inhibition functions of Tan I on radioresistant cancer
cells via a series of experiments. Results: Tan I significantly inhibited
cell proliferation and clone formation, consequently enhancing radiosensitivity
in radioresistant lung cancer cells, H358-IR and H157-IR. Stable isotope
labeling of amino acids in cell culture (SILAC)-based quantitative
proteomics indicated that Tan I downregulates expression of pro-oncogenic
protein phosphoribosyl pyrophosphate aminotransferase (PPAT) in both
H358-IR and H157-IR cells. Further analysis of molecular docking showed
that Tan I is well-docked into the active pocket of the structure
of PPAT, serving as a potential PPAT inhibitor. Conclusions: Taken
together, these findings suggest that inhibition of the tumor promoter
PPAT by Tan I exerts marked inhibitory effects on radioresistant lung
cancer cells, improving radiation efficacy.