NQO1 overexpression

CDFT and frontier molecular orbital analyses predicted the stability and reactivity of all the selected molecules. QSAR analysis predicted the biological activity and toxicity of the compounds. Withaferin A exhibited the highest glide gscore (-4.953 kcal/mol) and demonstrated 6 hydrogen bond interactions with NQO1, suggesting its potential as an anticancer agent. Conceptual density functional theory-based analysis suggested the strong electrophilicity of the ligands, further supporting their potential anticancer activities. Viscosalactone B, another phytochemical from Ashwagandha, also showed interactions involving 6 hydrogen bonds with NQO1, with a glide gscore of (-4.593 kcal/mol). Molecular dynamic simulations validated the stability of the Withaferin A-NQO1 complex. ADME-T properties predicted high oral absorption for the selected ligands, indicating that Withaferin A could be a viable orally administered drug.

On the one hand, I-HCy-Q can monitor the activity of NQO1 and distinguish the NQO1 positive cancer cells; on the other hand, the capacity of mitochondria-targeted photodynamic therapy makes I-HCy-Q an effective inducer of apoptosis and immunogenic cell death. Attribute to its complementary advantages, I-HCy-Q holds potential for the imaging and treatment of tumors in complex organisms.

The present in silico analysis suggests a possible alteration in resveratrol's orientation in the protein binding pocket. The findings encourage further investigation, including validation using in vitro and in vivo assays.

The high NQO1 expression in HCC cells impedes the lenvatinib-induced apoptosis by regulating the ROS levels, thereby promoting lenvatinib resistance in HCC cells.

The generalizability of the design is further demonstrated by engineering a HO-responsive PROTAC for specific degradation of HDAC6 in cells with elevated HO. The strategy of caging the ligand for target proteins would afford a new dimension for developing activatable PROTACs with high specificity and minimal side effects.

In conclusion, there existed a significant correlation between the CT image features and the expression level of NQO1, which could indirectly reflect the prognosis of patients with HCC. The predictive model based on arterial phase CT imaging features has good stability and diagnostic efficiency and is a potential means of identifying the expression level of NQO1 in HCC tissues before surgery.

By successfully self-assembling poly(ethylene glycol)-b-PMTC micelles, the model drug doxorubicin (DOX) was encapsulated with high efficiency...Overall, this study showcases the potential of MTC-based polycarbonate micelles to achieve targeted and specific drug release in the NQO1 enzyme-mediated tumor microenvironment. Therefore, the self-assembly of MTC-based polymers into nanomicelles holds immense promise as intelligent nanocarriers in drug delivery applications.

Snail knockdown could eliminate the promoting effect of ectopic NQO1 on the proliferation and invasion of GBM cells, and reduce its effects on the activity of PI3K/Akt/mTOR signaling pathway. These results indicated that NQO1 could promote GBM aggressiveness by activating the PI3K/Akt/mTOR signaling pathway in a Snail‑dependent manner, and NQO1 and its relevant pathways may be considered novel targets for GBM therapy.

Interestingly, the reduced migration and invasion by NQO1 knockdown were restored by FSCN1. Collectively, the loss of MEG3 upregulated NQO1, which in turn stabilized FSCN1 protein through its direct binding, resulting in elevated migration and invasion in arsenic-transformed cells.

Our findings identify CPT1A-dependent FAO as an essential metabolic pathway for NQO1 to promote the PAAD process. Targeting the NQO1/CPT1A/FAO axis in PAAD to attenuate proliferation and dissemination is a potential approach to promote a better antitumour effect and improve patient outcomes.

The reduction of NQO1-Luc could be triggered by NQO1, resulting in the release of free D-luciferin, and concomitantly a bright bioluminescence emission. NQO1-Luc exhibits high selectivity and sensitivity toward NQO1 activity and the capability of distinguishing NQO1-overexpressing cells in vitro and in vivo, which offers a promising tool for investigations of NQO1 related biological processes including tumors in living organisms.

In addition, Snail protein was stabilized by NQO1/p53/SREBP1 axis and triggered the EMT process, and participated in the regulatory role of NQO1/p53/SREBP1 axis in HCC. Together, these data indicated that NQO1/SREBP1 axis promoted the progression and metastasis of HCC, and might be a potential therapeutic target for HCC.