The most thorough safety analysis comes from a meta-analysis by Chen et al
Hence, we reconstructed condition-specific GSMMs containing only enzymes expressed in the study conditions
However, in the current experimental reports, due to the large heterogeneity between experiments, it is not possible to obtain the differences in drug responses of artemisinin and its derivatives in treating different subtypes of lung cancer (such as EGFR mutations and KRAS mutations) ( FIGURE 5 5.3.1 Suppressing inflammation and enhancing immunomodulation Artesunate inhibits NSCLC cell growth by inhibiting the TAZ/PD-L1 signaling and increasing CD8 + T cell infiltration ( + T lymphocyte counts in NSCLC ( 5.3.2 Antioxidant effects Artesunate activates the protective Keap1/Nrf2 pathway in lung cancer cells, improving cellular antioxidant defenses ( 5.3.3 Inhibition of cell proliferation and promotion of apoptosis Dihydroartemisinin inhibited the proliferation of A549/HCC 827 cell lines in a dose-dependent manner, and HCC 827 cells were more sensitive to dihydroartemisinin inhibition compared with A549 cells ( CASP-3 is upregulated after dihydroartemisinin intervention in A549-GR cells, whereas PARP and Bcl-2 are downregulated, alleviating gefitinib resistance and increasing apoptosis ( 5.3.4 Ferroptosis induction Dihydroartemisinin inhibits the downregulation of the expression of the ferroptosis-related proteins GPX4 and FTH in gefitinib-resistant A549 cells, thereby contributing to free iron release ( 5.3.5 Inhibition of cell invasion and migration Artesunate inhibits the proliferation, migration, and invasion of A549 and H1299 cells and induces their apoptosis, possibly due to reduced HuR and MMP-9 protein expressions ( 5.3.6 Cell cycle blockade Pyrrolidine inhibits the EGFR/PI3K/Akt signaling pathway, increases P21 expression, decreases cyclin B1 expression, and inhibits EGFR-dependent NSCLC cell growth and cell cycle blockade in the G2 phase ( 5.3.7 Autophagy inducing effect Autophagy was significantly upregulated in A549-GR cells after dihydroartemisinin treatment, and the expression of LC3 and Beclin1 (autophagy-related proteins) increased, while p62 decreased ( 5.3.8 Inhibition of angiogenesis Dihydroartemisinin inhibited tumor vascularization by decreasing the expression of HIF-1, VEGF, and endothelial cell-specific marker (CD31 and NG2) proteins, leading to a significant reduction in microvessel and mature vessel density in a time-dependent manner ( 5.3.9 Regulation of glycolysis Artesunate and dihydroartemisinin downregulate the extracellular signal-regulated kinase activity, inhibit c-Myc expression, and decrease glucose transporter protein (GLUT1), human myosin-releasing enzyme (HK 2), and lactate dehydrogenase A concentrations in a dose-dependent manner
Richter K, Paakkola T, Mennerich D, Kubaichuk K, Konzack A, Ali-Kippari H, Kozlova N, Koivunen P, Haapasaari KM, Jukkola-Vuorinen A, et al
(2) Martnez C, Juarranz Y, Gutirrez-Caas I, Carrin M, Prez-Garca S, Villanueva-Romero R, Castro D, Lamana A, Mellado M, Gonzlez-lvaro I, Gomariz RP
