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- W4386733910 abstract "Epidermal growth factor receptor (EGFR) and DNA topoisomerase II�(Topo II) are the key molecular targets for non-small cell lung cancer (NSCLC) due to its major contribution to complex signaling cascades modulating the survival of cancer cells. In the present study, mansonone G (MG), a naturally occurring quinone-containing compound, and its semi-synthetic ether derivatives were subjected to theoretically and experimentally investigate the anticancer effects on EGFR/Topo II-mediated signaling pathways in NSCLC cell lines expressing wild-type EGFR (A549) and mutant EGFR (H1975). In vitro cytotoxicity screening results demonstrated that butoxy MG (MG3) was more susceptible to H1975�mutant cells (IC50�of 4.21 ?M)�than A549 wild-type cells�(IC50 of 8.54 ?M). Importantly, MG3 was low toxic�against normal fibroblast cells (IC50 of 21.16 ?M). Western blotting and flow cytometric analyses revealed that MG3 induced�a caspase-dependent apoptosis mechanism through: (i) inhibition of p-STAT3 and p-Akt without affecting upstream p-EGFR and (ii) activation of p-Erk. According to the computational calculations on MGs/Topo II�complexes, we found that, among all studied MGs, an ester derivative MG14 exhibited�the highest binding affinity toward Topo II�ATPase domain. In addition, the binding of MG14 against Topo II�induced�the residues 147-151 to locate closer to ligand, resulting in a closed conformation. Additionally, the encapsulation of mansonones(s) into the hydrophobic inner cavity of beta-cyclodextrins�(?CDs), especially�2,6-dimethy-?CD derivative,�led to the enhancement of solubility, stability, enantioseparation, and anticancer activity of the uncomplexed mansonone(s)." @default.
- W4386733910 created "2023-09-15" @default.
- W4386733910 creator A5027050921 @default.
- W4386733910 date "2023-09-14" @default.
- W4386733910 modified "2023-09-26" @default.
- W4386733910 title "Anticancer activity of mansonone G derivatives against human non-small cell lung cancer: computational and mechanistic study" @default.
- W4386733910 doi "https://doi.org/10.58837/chula.the.2018.11" @default.
- W4386733910 hasPublicationYear "2023" @default.
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