PMID- 38532833
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240328
IS  - 2211-8020 (Print)
IS  - 2211-8039 (Electronic)
IS  - 2211-8020 (Linking)
VI  - 13
IP  - 4
DP  - 2023
TI  - Efficacy of HMJ-38, a new quinazolinone analogue, against the 
      gemcitabine-resistant MIA-PaCa-2 pancreatic cancer cells.
PG  - 20-31
LID - 10.37796/2211-8039.1423 [doi]
AB  - 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.
CI  - (c) the Author(s).
FAU - Hour, Mann-Jen
AU  - Hour MJ
AD  - School of Pharmacy, China Medical University, Taichung, 406040, Taiwan.
FAU - Tsai, Fuu-Jen
AU  - Tsai FJ
AD  - School of Chinese Medicine, College of Chinese Medicine, China Medical 
      University, Taichung, 404333, Taiwan.
AD  - Human Genetics Center, Department of Medical Research, China Medical University 
      Hospital, Taichung, 404327, Taiwan.
AD  - Department of Medical Genetics, China Medical University Hospital, Taichung, 
      404327, Taiwan.
FAU - Lai, I-Lu
AU  - Lai IL
AD  - Cell Therapy Center, China Medical University Hospital, Taichung, 404327, Taiwan.
FAU - Tsao, Je-Wei
AU  - Tsao JW
AD  - School of Pharmacy, China Medical University, Taichung, 406040, Taiwan.
FAU - Chiang, Jo-Hua
AU  - Chiang JH
AD  - Department of Nursing, Chung-Jen Junior College of Nursing, Health Sciences and 
      Management, Chiayi, 62201, Taiwan.
FAU - Chiu, Yu-Jen
AU  - Chiu YJ
AD  - Division of Plastic and Reconstructive Surgery, Department of Surgery, Taipei 
      Veterans General Hospital, Taipei, 112201, Taiwan.
AD  - Department of Surgery, School of Medicine, National Yang Ming Chiao Tung 
      University, Taipei, 112304, Taiwan.
AD  - Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, 
      112304, Taiwan.
FAU - Lu, Hsing-Fang
AU  - Lu HF
AD  - Department of Medical Research, China Medical University Hospital, China Medical 
      University, Taichung, 404327, Taiwan.
FAU - Juan, Yu-Ning
AU  - Juan YN
AD  - Department of Medical Research, China Medical University Hospital, China Medical 
      University, Taichung, 404327, Taiwan.
FAU - Yang, Jai-Sing
AU  - Yang JS
AD  - Department of Medical Research, China Medical University Hospital, China Medical 
      University, Taichung, 404327, Taiwan.
FAU - Tsai, Shih-Chang
AU  - Tsai SC
AD  - Department of Biological Science and Technology, China Medical University, 
      Taichung, 406040, Taiwan.
LA  - eng
PT  - Journal Article
DEP - 20231201
PL  - China (Republic : 1949- )
TA  - Biomedicine (Taipei)
JT  - BioMedicine
JID - 101611451
PMC - PMC10962539
OTO - NOTNLM
OT  - Apoptotic cell death
OT  - Autophagy
OT  - Epidermal growth factor receptor (EGFR)
OT  - Gemcitabine-resistance MIA-PaCa-2 pancreatic cancer cells (MIA-GR100)
OT  - HMJ-38
COIS- Conflict of interest: The authors declare that they have no competing interests.
EDAT- 2024/03/27 06:44
MHDA- 2024/03/27 06:45
PMCR- 2023/12/01
CRDT- 2024/03/27 03:46
PHST- 2023/07/04 00:00 [received]
PHST- 2023/08/15 00:00 [accepted]
PHST- 2024/03/27 06:45 [medline]
PHST- 2024/03/27 06:44 [pubmed]
PHST- 2024/03/27 03:46 [entrez]
PHST- 2023/12/01 00:00 [pmc-release]
AID - bmed-13-04-020 [pii]
AID - 10.37796/2211-8039.1423 [doi]
PST - epublish
SO  - Biomedicine (Taipei). 2023 Dec 1;13(4):20-31. doi: 10.37796/2211-8039.1423. 
      eCollection 2023.