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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1403424
This article is part of the Research Topic Innovative Approaches to Overcome Resistance and Toxicities of Anti-Cancer Drugs View all 14 articles

The SAR analysis of Dietary Polyphenols and their Antagonistic Effects on Bortezomib at Physiological Concentrations

Provisionally accepted
Tran Tran T. Van Tran Tran T. Van 1Hsun-Shuo Chang Hsun-Shuo Chang 1Ho-Cheng Wu Ho-Cheng Wu 2Chung-Kuang Lu Chung-Kuang Lu 3Hui-Chi Huang Hui-Chi Huang 4Michal Korinek Michal Korinek 1Hui-Hua Hsiao Hui-Hua Hsiao 5*Chia-Hung Yen Chia-Hung Yen 6*
  • 1 Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
  • 2 Graduate Institute of Pharmacognosy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan
  • 3 College of Life Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan
  • 4 China Medical University (Taiwan), Taichung, Taiwan
  • 5 Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
  • 6 Kaohsiung Medical University, Kaohsiung, Taiwan

The final, formatted version of the article will be published soon.

    Bortezomib (BTZ), a primary treatment for MM, but its effectiveness can be reduced by interactions with vicinal diol moieties (VDMs) in polyphenols. Despite this, it’s debated whether BTZ therapy necessitates avoiding polyphenol-rich products, given the low bioavailability of polyphenols. Additionally, it remains unclear whether the structure of polyphenols contributes to their BTZ antagonism. Therefore, our study aims to unravel the structure-activity relationship of dietary polyphenols and their BTZ antagonism at daily diet-achievable physiological concentrations. By cell viability assays, we found a positive correlation between the number of VDMs in gallotannins and their BTZ antagonism. Moreover, the origin and configuration of VDMs, rather than the total VDM concentration, play a pivotal role in the combined antagonistic effects against BTZ in gallotannins. Additionally, ChemGPS-NP analysis indicated that the aromaticity and C-3 hydroxyl group in flavonoids' C-rings enhance their BTZ antagonism. Finally, long-term cytotoxicity assays reveal that gallic acid (GA), epigallocatechin (EGC), and epigallocatechin gallate (EGCG), at their physiological concentrations—attainable through tea consumption—significantly and synergistically antagonize BTZ. Therefore, due to the potential for these polyphenols to reduce the effectiveness of BTZ, it is advisable for MM patients undergoing BTZ treatment to reduce their consumption of foods high in VDM-containing polyphenols.

    Keywords: Multiple Myeloma, boronic acid-based proteasome inhibitor, Bortezomib, polyphenol, vicinal diol moieties, Physiological concentrations

    Received: 19 Mar 2024; Accepted: 12 Jul 2024.

    Copyright: © 2024 Van, Chang, Wu, Lu, Huang, Korinek, Hsiao and Yen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Hui-Hua Hsiao, Kaohsiung Medical University Hospital, Kaohsiung, 80756, Taiwan
    Chia-Hung Yen, Kaohsiung Medical University, Kaohsiung, Taiwan

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