2. Academic Validation
  3. Proteostasis Disruption by Proteasome Inhibitor MG132 and Propolin G Induces ER Stress- and Autophagy-Mediated Apoptosis in Breast Cancer

Proteostasis Disruption by Proteasome Inhibitor MG132 and Propolin G Induces ER Stress- and Autophagy-Mediated Apoptosis in Breast Cancer

  • Food Sci Nutr. 2025 Jul 13;13(7):e70632. doi: 10.1002/fsn3.70632.
Jih-Tung Pai 1,  Lei-Po Chen 2 3,  Hsuan-Jui Chang 4,  Shih-Wei Wang 5 6,  Yann-Lii Leu 7 8,  Cheng-Ta Lai 2 9,  Meng-Shih Weng 4
Affiliations

Affiliations

  • 1 Division of Hematology and Oncology Tao-Yuan General Hospital, Ministry of Health and Welfare Taoyuan City Taiwan.
  • 2 Department of Medicine MacKay Medical College New Taipei City Taiwan.
  • 3 Division of Spine Surgery, Department of Orthopedic Surgery MacKay Memorial Hospital New Taipei City Taiwan.
  • 4 Department of Nutritional Science Fu Jen Catholic University New Taipei City Taiwan.
  • 5 Institute of Biomedical Sciences MacKay Medical College New Taipei City Taiwan.
  • 6 Graduate Institute of Natural Products, College of Pharmacy Kaohsiung Medical University Kaohsiung City Taiwan.
  • 7 Graduate Institute of Natural Products, College of Medicine Chang Gung University Taoyuan City Taiwan.
  • 8 BioBank Chang Gung Memorial Hospital at Linkou Taoyuan City Taiwan.
  • 9 Division of Colon and Rectal Surgery, Department of Surgery MacKay Memorial Hospital Taipei Taiwan.
PMID: 40661805 DOI: 10.1002/fsn3.70632
Abstract

The maintenance of protein homeostasis, commonly referred to as proteostasis, is critical for the proper functioning of cells. Disruptions in protein degradation pathways can result in proteotoxic stress, which may ultimately lead to cellular Apoptosis. Targeting the dysregulation of proteostasis has emerged as a promising approach in Cancer therapy. Propolin G, a c-prenylflavanone derived from Taiwanese propolis, has demonstrated Anticancer properties; however, its underlying mechanisms remain largely unexplored. In this study, we evaluated the combined effect of propolin G and the Proteasome Inhibitor MG132 on breast Cancer cells. While individual treatments with MG132 (1 μM) or propolin G (10 μM) exhibited minimal effects on cell viability, their combination resulted in a synergistic suppression of proliferation and induction of Apoptosis, as indicated by a combination index (CI) of 0.63. This combined treatment significantly reduced Proteasome activity, leading to the accumulation of polyubiquitinated proteins. Mechanistically, Apoptosis was mediated through the activation of the PERK/ATF4/CHOP signaling pathway and Autophagy, as evidenced by increased expression levels of ULK1, Beclin1, ATG5, and LC3-II. These findings highlight the potential of targeting proteostasis disruption as an effective Anticancer strategy in breast Cancer. The combination of propolin G and MG132 may leverage cancer-specific vulnerabilities and possess translational potential for Anticancer therapy.

Keywords

autophagy; propolin G; proteasome inhibitor; protein homeostasis.

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