The Therapeutic Role of PNU-74654 in Hepatocellular Carcinoma May Involve Suppression of NF-κB Signaling

  • Medicina (Kaunas). 2022 Jun 14;58(6):798. doi: 10.3390/medicina58060798.
Min-You Wu  1 ,  Chi-Chih Wang  1  2 ,  Ya-Chuan Chang  1 ,  Chia-Ying Yu  1 ,  Wen-Wei Sung  1  3  4 ,  Chih-Jung Chen  1  2  3  5 ,  Ming-Chang Tsai  1  2
Affiliations
  • 1. School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan.
  • 2. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung 402, Taiwan.
  • 3. Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan.
  • 4. Department of Urology, Chung Shan Medical University Hospital, Taichung 402, Taiwan.
  • 5. Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung 407, Taiwan.
PMID: 35744061 DOI: 10.3390/medicina58060798
Abstract

Background and Objectives: PNU-74654, a Wnt/β-catenin Inhibitor, has reported antitumor activities; however, the therapeutic potential of PNU-74654 in hepatocellular carcinoma (HCC) has not been investigated in detail. The aim of this study was to clarify the cytotoxic effects of PNU-74654 against HCC and to uncover its molecular mechanism. Materials and Methods: HepG2 and Huh7 liver Cancer cell lines were selected to determine the antitumor properties of PNU-74654. Survival of the liver Cancer cells in response to PNU-74654 was assessed by cell viability assays, and the Apoptosis effect of PNU-74654 was analyzed by flow cytometry and visualized by Hoechst staining. An oncology array was used to explore the underlying molecular routes of PNU-74654 action in the cells. The migration properties were examined with a wound healing assay, and western blotting was conducted to evaluate protein expression. Results: Treatment with PNU-74654 decreased cell viability and inhibited cell migration. The cell cycle analysis and Hoechst staining revealed an increase in the population of cells at the sub-G1 stage and apoptotic morphological changes in the nucleus. The oncology array identified 84 oncology-related proteins and a suppressed expression of Bcl-xL and Survivin. Western blotting showed that PNU-74654 could interfere with cell cycle-related proteins through the NF-κB pathway. Conclusions: PNU-74654 shows antiproliferative and antimigration effects against HepG2 and Huh7 cells, and its antitumor activity may be attributable to its interference in cell cycle regulation and the NF-κB pathway.

Keywords
NF-κB; PNU-74654; apoptosis; cyclin A; hepatocellular carcinoma.
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