PW06 Triggered Fas-FADD to Induce Apoptotic Cell Death In Human Pancreatic Carcinoma MIA PaCa-2 Cells through the Activation of the Caspase-Mediated Pathway.

Autor: Huang YP; Department of Physiology, School of Medicine, China Medical University, Taichung 404333, Taiwan., Hsia TC; Department of Medical Research, China Medical University Hospital, Taichung 404333, Taiwan.; Department of Respiratory Therapy, China Medical University, Taichung 404333, Taiwan., Yeh CA; Department of Physiology, School of Medicine, China Medical University, Taichung 404333, Taiwan., Ma YS; School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung 84001, Taiwan.; Department of Chinese Medicine, E-Da Hospital, Kaohsiung 82385, Taiwan., Hsu SY; Department of Ophthalmology, An Nan Hospital, China Medical University, Tainan 709, Taiwan.; Department of Optometry, Chung Hwa University of Medical Technology, Tainan 717302, Taiwan., Liu YC; Institute of Population Health Sciences, National Health Research Institutes, Miaoli 350, Taiwan., Lyu PC; Institute of Bioinformatics and Structural Biology, National Tsing-Hua University, Hsinchu 300044, Taiwan., Lai KC; Department of Medical Laboratory Science and Biotechnology, College of Medical Technology, Chung Hwa University of Medical Technology, Tainan, Taiwan., Peng SF; Department of Biological Science and Technology, China Medical University, Taichung 406040, Taiwan.; Department of Internal Medicine, China Medical University Hospital, Taichung 404333, Taiwan., Lien JC; School of Pharmacy, China Medical University, Taichung 406040, Taiwan., Hsieh WT; Chinese Medicine Research Center, China Medical University, Taichung 404333, Taiwan.; Department of Pharmacology, China Medical University, Taichung 404333, Taiwan.
Jazyk: angličtina
Zdroj: Oxidative medicine and cellular longevity [Oxid Med Cell Longev] 2023 Feb 11; Vol. 2023, pp. 3479688. Date of Electronic Publication: 2023 Feb 11 (Print Publication: 2023).
DOI: 10.1155/2023/3479688
Abstrakt: Pancreatic cancer has higher incidence and mortality rates worldwide. PW06 [(E)-3-(9-ethyl-9H-carbazol-3-yl)-1-(2,5-dimethoxyphenyl) prop-2-en-1-one] is a carbazole derivative containing chalcone moiety which was designed for inhibiting tumorigenesis in human pancreatic cancer. This study is aimed at investigating PW06-induced anticancer effects in human pancreatic cancer MIA PaCa-2 cells in vitro . The results showed PW06 potent antiproliferative/cytotoxic activities and induced cell morphological changes in a human pancreatic cancer cell line (MIA PaCa-2), and these effects are concentration-dependent (IC 50 is 0.43  μ M). Annexin V and DAPI staining assays indicated that PW06 induced apoptotic cell death and DNA condensation. Western blotting indicated that PW06 increased the proapoptotic proteins such as Bak and Bad but decreased the antiapoptotic protein such as Bcl-2 and Bcl-xL. Moreover, PW06 increased the active form of caspase-8, caspase-9, and caspase-3, PARP, releasing cytochrome c, AIF, and Endo G from mitochondria in MIA PaCa-2 cells. Confocal laser microscopy assay also confirmed that PW06 increased Bak and decreased Bcl-xL. Also, the cells were pretreated with inhibitors of caspase-3, caspase-8, and caspase-9 and then were treated with PW06, resulting in increased viable cell number compared to PW06 treated only. Furthermore, PW06 showed a potent binding ability with hydrophobic interactions in the core site of the Fas-Fas death domains (FADD). In conclusion, PW06 can potent binding ability to the Fas-FADD which led to antiproliferative, cytotoxic activities, and apoptosis induction accompanied by the caspase-dependent and mitochondria-dependent pathways in human pancreatic cancer MIA PaCa-2 cells.
Competing Interests: The authors have no conflicts of interest to disclose.
(Copyright © 2023 Yi-Ping Huang et al.)
Databáze: MEDLINE
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