Mann-Jen Hour, School of Pharmacy, China Medical University, Taichung 406040, Taiwan
Fuu‑ Jen Tsai, School of Chinese Medicine, College of Chinese Medicine, China Medical University; Taichung 404333, Taiwan
I-Lu Lai, Cell Therapy Center, China Medical University Hospital, Taichung 404327, Taiwan
Je-Wei Tsao, School of Pharmacy, China Medical University, Taichung 406040, Taiwan
Jo-Hua Chiang, Department of Nursing, Chung-Jen Junior College of Nursing, Health Sciences and Management, Chiayi 62201, Taiwan
Yu-Jen Chiu, Department of Nursing, Chung-Jen Junior College of Nursing, Health Sciences and Management, Chiayi 62201, Taiwan.
Hsing-Fang Lu, Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, 404327, Taiwan
Yu‑ Ning Juan, Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, 404327, Taiwan
Jai-Sing Yang, Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, 404327, TaiwanFollow
Shih-Chang Tsai, Department of Biological Science and Technology, China Medical University, Taichung, 406040, TaiwanFollow

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 (MIAGR100) 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, or 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 functions as a

cytoprotective mechanism. MIA-GR100 cells treated with both zVADFMK and HMJ-38 were much more viable than those treated with HMJ-38 alone. HMJ-38 promotes apoptosis in MIA-GR100 cells by activating caspase. Epidermal growth factor receptor

(EGFR) is one of HMJ-38's principal targets, as determined via in silico target screening and 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.

Hour, Mann-Jen; Tsai, Fuu‑ Jen; Lai, I-Lu; Tsao, Je-Wei; Chiang, Jo-Hua; Chiu, Yu-Jen; Lu, Hsing-Fang; Juan, Yu‑ Ning; Yang, Jai-Sing; and Tsai, Shih-Chang (2023) "Efficacy of HMJ-38, a new quinazolinone analogue, against the gemcitabine-resistant MIA-PaCa-2 pancreatic cancer cells," BioMedicine: Vol. 13 : Iss. 4 , Article 3.
DOI: 10.37796/2211-8039.1423