Efficacy of HMJ-38, a new quinazolinone analogue, against the gemcitabine-resistant MIA-PaCa-2 pancreatic cancer cells

Abstract

Gemcitabine is frequently utilized to treat pancreatic cancer. The purpose of our study was to create a gemcitabine-resistant MIA-PaCa-2 pancreatic cancer cell line (MIA-GR100) and to evaluate the anti-pancreatic cancer efficacy of HMJ-38, a new quinazolinone analogue. Compared to their parental counterparts, MIA-PaCa-2, established MIA-GR100 cells were less sensitive to gemcitabine. MIA-GR100 cell viability was not affected by 10, 50 and 100 nM gemcitabine concentrations. HMJ-38 reduced MIA-GR100 cell growth and induced autophagy and apoptosis. When stained with monodansylcadaverine (MDC), acridine orange (AO), and terminal deoxynucleotide transferase dUTP nick end labeling (TUNEL), MIA-GR100 cells shrunk, punctured their membranes, and produced autophagy vacuoles and apoptotic bodies. Combining chloroquine (CQ) and 3-methyladenine (3-MA) with HMJ-38 dramatically reduced cell viability, indicating that autophagy function as a cytoprotective mechanism. MIA-GR100 cells treated with both z-VAD-FMK and HMJ-38 were much more viable than those treated with HMJ-38 alone. HMJ-38 promotes apoptosis in MIA-GR100 cells by activating caspases. Epidermal growth factor receptor (EGFR) is one of HMJ-38’s principal targets, as determined via in silico target screening with network prediction. HMJ-38 also inhibited EGFR kinase activity and EGFR-associated signaling in MIA-GR100 cells. HMJ-38 may be an effective chemotherapeutic adjuvant for gemcitabine-resistant pancreatic cancer cells, in which it induces an antitumor response.

Ohwia caudata aqueous extract attenuates senescence in aging adipose-derived mesenchymal stem cells

“…Cell proliferation was quantified using the MTT assay [ 33 ]. The hADMSCs (passage 8) were seeded in 96-well plates and exposed to various concentrations of O. caudata aqueous extract (12.5–800 μg/ml) for 24–72 h. Then, the culture medium was replaced with 100 μl of MTT (0.5 mg/ml) and incubated at 37 °C for 4 h. Subsequently, the excess medium was removed by suction, and the resulting purple formazan was dissolved in 100 μl of dimethyl sulfoxide with gentle shaking in the dark for 15 min.…”