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      Intralesional Chemotherapy for Prostate Cancer: In vivo Proof of Principle

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          Abstract

          Introduction: Prostate cancer (PCA) is one of the most common cancers in the world, and current therapies are debilitating to patients. To develop a novel modality for the treatment of PCA, we evaluated the efficacy of intralesional administration of the Sirt3 activator Honokiol (HK) and the NADPH oxidase inhibitor Dibenzolium (DIB). Methods: We used a well-established transgenic adenocarcinoma mouse prostate (TRAMP-C2) model of hormone-independent PCA. MTS assay, apoptosis assay, wound healing assay, transwell invasion assay, RT-qPCR, and Western blotting were conducted in vitro, and HK and DIB were intratumorally administered to mice bearing TRAMP-C2 tumors. Tumor size and weight were observed over time. After removing tumors, H-E staining and immunohistochemistry (IHC) staining were conducted. Results: Treatment by HK or DIB showed an inhibitory effect on cell proliferation and migration in PCA cells. Poor ability to induce apoptosis in vitro, insufficient expression of caspase-3 on IHC staining, and increased necrotic areas on H-E staining indicated that necrosis plays an important role in cell death in treating groups by HK or DIB. RT-PCR, Western blotting, and IHC staining for epithelial mesenchymal transition (EMT) markers suggested that EMT was suppressed by HK and DIB individually. In addition, HK induced activation of CD3. Mouse experiments showed safe antitumor effects in vivo. Conclusions: HK and DIB suppressed PCA proliferation and migration. Further research will explore the effects of HK and DIB at the molecular level to reveal new mechanisms that can be exploited as therapeutic modalities.

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          Author and article information

          Journal
          OCL
          Oncology
          10.1159/issn.0030-2414
          Oncology
          Oncology
          S. Karger AG
          0030-2414
          1423-0232
          2023
          October 2023
          26 June 2023
          : 101
          : 10
          : 645-654
          Affiliations
          [_a] aDepartment of International Health, Kobe University Graduate School of Health Sciences, Kobe, Japan
          [_b] bDepartment of Urology, Kobe University Graduate School of Medicine, Kobe, Japan
          [_c] cDepartment of Medical Innovation Engineering, Kobe University Graduate School of Medicine, Kobe, Japan
          [_d] dMetroderm United Derm Partners, Atlanta, Georgia, USA
          Author information
          https://orcid.org/0000-0001-5027-3822
          Article
          531494 Oncology 2023;101:645–654
          10.1159/000531494
          37364538
          b8e5cecd-cd92-4a40-ade2-87334b46830e
          © 2023 S. Karger AG, Basel

          Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.

          History
          : 14 October 2022
          : 07 June 2023
          Page count
          Figures: 5, Tables: 1, Pages: 10
          Funding
          This research received no external funding.
          Categories
          Clinical Translational Research

          Medicine
          Apoptosis,Honokiol,Prostate cancer,Epithelial mesenchymal transition,Necrosis,Dibenzolium
          Medicine
          Apoptosis, Honokiol, Prostate cancer, Epithelial mesenchymal transition, Necrosis, Dibenzolium

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