Epidermal growth factor receptor (EGFR), overexpressed in many types of cancer, has been proved as a high potential target for targeted cancer therapy due to its role in regulating proliferation and survival of cancer cells. In the present study, a series of designed vinyl sulfone derivatives was screened against EGFR tyrosine kinase (EGFR-TK) using in silico and in vitro studies. The molecular docking results suggested that, among 78 vinyl sulfones, there were eight compounds that could interact well with the EGFR-TK at the ATP-binding site. Afterwards, these screened compounds were tested for the inhibitory activity towards EGFR-TK using ADP-Glo™ kinase assay, and we found that only VF16 compound exhibited promising inhibitory activity against EGFR-TK with the IC₅₀ value of 7.85 ± 0.88 nM. In addition, VF16 showed a high cytotoxicity with IC₅₀ values of 33.52 ± 2.57, 54.63 ± 0.09, and 30.38 ± 1.37 µM against the A431, A549, and H1975 cancer cell lines, respectively. From 500-ns MD simulation, the structural stability of VF16 in complex with EGFR-TK was quite stable, suggesting that this compound could be a novel small molecule inhibitor targeting EGFR-TK.

Epidermal growth factor receptor (EGFR) is a member of the ErbB family of proteins and are involved in downstream signal transduction, plays prominent roles in cell growth regulation, proliferation, and the differentiation of many cell types. They are correlated with the stage and severity of cancer. Therefore, EGFRs are targeted proteins for the design of new drugs to treat cancers that overexpress these proteins. Currently, several bioactive natural extracts are being studied for therapeutic purposes. Cannabis has been reported in many studies to have beneficial medicinal effects, such as anti-inflammatory, analgesic, antibacterial, and anti-inflammatory effects, and antitumor activity. However, it is unclear whether cannabinoids reduce intracellular signaling by inhibiting tyrosine kinase phosphorylation. In this study, cannabinoids (CBD, CBG, and CBN) were simulated for binding to the EGFR-intracellular domain to evaluate the binding energy and binding mode based on molecular docking simulation. The results showed that the binding site was almost always located at the kinase active site. In addition, the compounds were tested for binding affinity and demonstrated their ability to inhibit kinase enzymes. Furthermore, the compounds potently inhibited cellular survival and apoptosis induction in either of the EGFR-overexpressing cell lines.

Phallus indusiatus, or bamboo mushroom, has been reported for its nutraceutical properties, while its cosmeceutical properties remain unclear. In this study, we conducted extractions of whole, fresh P. indusiatus using both aqueous and ethanolic methods. Among the extracts, ultrasonic-assisted extraction method with DI showed the highest antioxidant activity compared to the others. For cosmeceutical assessment, we evaluated the extracts’ inhibitory effects against ECM-degrading enzymes and found that they exhibited a modest inhibitory effect of approximately 50%. Remarkably, ultrasonic-assisted extraction with DI demonstrated promising cosmeceutical properties. Additionally, pressure-assisted extraction with DI showed a potentially protective effect against H₂O₂-induced DNA damage. To investigate the anti-melanogenic effect on MNT-1 cells, we treated them with the extracts and observed a significant decrease in cellular tyrosinase activity under α-MSH stimulation. This resulted in a relative reduction in melanin content. Notably, autoclaving extraction exhibited a significantly greater anti-melanogenic effect than the other extracts at the lowest concentration tested. Furthermore, the extracts demonstrated a reduction in NO production under LPS-induced inflammation. Hot water extraction with DI and ethanol exhibited a stronger anti-inflammatory effect compared to diclofenac, without any cytotoxicity. These findings highlight the hidden cosmeceutical properties of P. indusiatus and suggest its potential use as a bioactive ingredient in cosmetic formulations.

Janus kinases (JAKs) are involved in numerous cellular signaling processes related to immune cell functions. JAK2 and JAK3 are associated with the pathogenesis of leukemia and common lymphoid-derived illnesses. JAK2/3 inhibitors could reduce the risk of various diseases by targeting this pathway. Herein, the naphthoquinones were experimentally and theoretically investigated to identify novel JAK2/3 inhibitors. Napabucasin and 2′-methyl napabucasin exhibited potent cell growth inhibition in TF1 (IC₅₀ = 9.57 and 18.10 μM) and HEL (IC₅₀ = 3.31 and 6.65 μM) erythroleukemia cell lines, and they significantly inhibited JAK2/3 kinase activity (in a nanomolar range) better than the known JAK inhibitor, tofacitinib. Flow cytometric analysis revealed that these two compounds induced apoptosis in TF1 cells in a time and dose-dependent manner. From the molecular dynamics study, both compounds formed hydrogen bonds with Y931 and L932 residues and hydrophobically contacted with the conserved hinge region, G loop, and catalytic loop of the JAK2. Our obtained results suggested that napabucasin and its methylated analog were potential candidates for further development of novel anticancer drug targeting JAKs.

Objective: To evaluate the anti-inflammatory and anticancer effects of Phallus indusiatus extracts, particularly in modulating inflammatory microenvironments and sensitizing lapatinib-induced cytotoxicity in breast cancer cells. Methods: Phallus indusiatus (bamboo mushroom) extracts were prepared using water extraction from fresh and dried specimens. The anti-inflammatory effects were assessed using RAW246.7 cells by measuring NO production, while cytotoxicity and proliferation effects were evaluated in MCF-7 and MCF-10A breast cell lines. To mimic the inflammatory microenvironment of breast cancer, MCF-7 cells were treated with TNFα to induce lapatinib resistance. The effects of the extracts on cell viability, apoptosis, and NF-kappaB signaling were evaluated under inflammatory microenvironment-mimicking conditions. Co-treatment with lapatinib and the extracts was analyzed for synergistic cytotoxic effects and pathway modulation. Results: P. indusiatus extracts demonstrated anti-inflammatory effects by reducing NO production in RAW246.7 cells. The extracts showed no cytotoxicity on MCF-7 and MCF-10A cells, with an observed proliferation increase in MCF-10A but not MCF-7. Under inflammatory microenvironment-mimicking conditions induced by TNFα, the extracts slightly reduced MCF-7 cell viability in a dose-dependent manner. Additionally, the extracts sensitized lapatinib-induced cytotoxicity by increasing apoptotic cell populations. Mechanistically, co-treatment with the extracts attenuated AKT and NF-kappaB activation in a dose-dependent manner. Conclusion: These findings highlight the potential of P. indusiatus extracts as supplementary food for breast cancer patients, particularly in inflammatory microenvironment conditions.