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ORIGINAL RESEARCH article

Front. Oncol.
Sec. Genitourinary Oncology
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1431362

Targeting Heme Degradation Pathway Augments Prostate Cancer Cell Sensitivity to Docetaxel-Induced Apoptosis and Attenuates Migration

Provisionally accepted
Ramia J. Salloom Ramia J. Salloom Iman M. Ahmad Iman M. Ahmad Maher Y. Abdalla Maher Y. Abdalla *
  • University of Nebraska Medical Center, Omaha, United States

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

    Chemotherapy, notably docetaxel (Doc), stands as the primary treatment for castration-resistant prostate cancer (CRPC). However, its efficacy is hindered by side effects and chemoresistance. Hypoxia in prostate cancer (PC) correlates with chemoresistance to Doc-induced apoptosis via Heme Oxygenase-1 (HO-1) modulation, a key enzyme in heme metabolism. This study investigated targeting heme degradation pathway via HO-1 inhibition to potentiate the therapeutic efficacy of Doc in PC. Utilizing diverse PC cell lines, we evaluated HO-1 inhibition alone and with Doc on viability, apoptosis, migration, and epithelial-to-mesenchymal transition (EMT) markers and elucidated the underlying mechanisms. HO-1 inhibition significantly reduced PC cell viability under hypoxic and normoxic conditions, enhancing Doc-induced apoptosis through interconnected mechanisms, including elevated reactive oxygen species (ROS) levels, glutathione cycle disruption, and modulation of Signal Transducer and Activator of Transcription 1 (STAT1) pathway. The interplay between STAT1 and HO-1 suggests its reliance on HO-1 activation. Additionally, a decrease in cell migration and downregulation of EMT markers (vimentin and snail) were observed, indicating attenuation of mesenchymal phenotype. In conclusion, the combination of HO-1 inhibition with Doc holds promise for improving therapeutic outcomes and advancing clinical management in PC.

    Keywords: Heme oxygenase-1 (HO-1), Prostate cancer (PC), SnPP (CID: 73755113), Znpp, DOCETAXEL, STAT 1, Snail, Vimentin

    Received: 11 May 2024; Accepted: 02 Jul 2024.

    Copyright: © 2024 Salloom, Ahmad and Abdalla. 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: Maher Y. Abdalla, University of Nebraska Medical Center, Omaha, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.