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Non-oncology drug (meticrane) shows anti-cancer ability in synergy with epigenetic inhibitors and appears to be involved passively in targeting cancer cells

Emerging evidence suggests that chemotherapeutic agents and targeted anticancer drugs have serious side effects on the healthy cells/tissues of the patient. To overcome this, the use of non-oncology drugs as potential cancer therapies has been gaining momentum. Herein, we investigated one non-oncolo...

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Autores principales: Wang, Yulu, Sharma, Amit, Ge, Fangfang, Chen, Peng, Yang, Yu, Liu, Hongjia, Liu, Hongde, Zhao, Chunxia, Mittal, Lovika, Asthana, Shailendra, Schmidt-Wolf, Ingo G. H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10235775/
https://www.ncbi.nlm.nih.gov/pubmed/37274234
http://dx.doi.org/10.3389/fonc.2023.1157366
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author Wang, Yulu
Sharma, Amit
Ge, Fangfang
Chen, Peng
Yang, Yu
Liu, Hongjia
Liu, Hongde
Zhao, Chunxia
Mittal, Lovika
Asthana, Shailendra
Schmidt-Wolf, Ingo G. H.
author_facet Wang, Yulu
Sharma, Amit
Ge, Fangfang
Chen, Peng
Yang, Yu
Liu, Hongjia
Liu, Hongde
Zhao, Chunxia
Mittal, Lovika
Asthana, Shailendra
Schmidt-Wolf, Ingo G. H.
author_sort Wang, Yulu
collection PubMed
description Emerging evidence suggests that chemotherapeutic agents and targeted anticancer drugs have serious side effects on the healthy cells/tissues of the patient. To overcome this, the use of non-oncology drugs as potential cancer therapies has been gaining momentum. Herein, we investigated one non-oncology drug named meticrane (a thiazide diuretic used to treat essential hypertension), which has been reported to indescribably improve the therapeutic efficacy of anti-CTLA4 in mice with AB1 HA tumors. In our hypothesis-driven study, we tested anti-cancer potential meticrane in hematological malignance (leukemia and multiple myeloma) and liver cancer cell lines. Our analysis showed that: 1) Meticrane induced alteration in the cell viability and proliferation in leukemia cells (Jurkat and K562 cells) and liver cancer (SK-hep-1), however, no evidence of apoptosis was detectable. 2) Meticrane showed additive/synergistic effects with epigenetic inhibitors (DNMT1/5AC, HDACs/CUDC-101 and HDAC6/ACY1215). 3) A genome-wide transcriptional analysis showed that meticrane treatment induces changes in the expression of genes associated with non-cancer associated pathways. Of importance, differentially expressed genes showed favorable correlation with the survival-related genes in the cancer genome. 4) We also performed molecular docking analysis and found considerable binding affinity scores of meticrane against PD-L1, TIM-3, CD73, and HDACs. Additionally, we tested its suitability for immunotherapy against cancers, but meticrane showed no response to the cytotoxicity of cytokine-induced killer (CIK) cells. To our knowledge, our study is the first attempt to identify and experimentally confirm the anti-cancer potential of meticrane, being also the first to test the suitability of any non-oncology drug in CIK cell therapy. Beyond that, we have expressed some concerns confronted during testing meticrane that also apply to other non-oncology drugs when considered for future clinical or preclinical purposes. Taken together, meticrane is involved in some anticancer pathways that are passively targeting cancer cells and may be considered as compatible with epigenetic inhibitors.
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spelling pubmed-102357752023-06-03 Non-oncology drug (meticrane) shows anti-cancer ability in synergy with epigenetic inhibitors and appears to be involved passively in targeting cancer cells Wang, Yulu Sharma, Amit Ge, Fangfang Chen, Peng Yang, Yu Liu, Hongjia Liu, Hongde Zhao, Chunxia Mittal, Lovika Asthana, Shailendra Schmidt-Wolf, Ingo G. H. Front Oncol Oncology Emerging evidence suggests that chemotherapeutic agents and targeted anticancer drugs have serious side effects on the healthy cells/tissues of the patient. To overcome this, the use of non-oncology drugs as potential cancer therapies has been gaining momentum. Herein, we investigated one non-oncology drug named meticrane (a thiazide diuretic used to treat essential hypertension), which has been reported to indescribably improve the therapeutic efficacy of anti-CTLA4 in mice with AB1 HA tumors. In our hypothesis-driven study, we tested anti-cancer potential meticrane in hematological malignance (leukemia and multiple myeloma) and liver cancer cell lines. Our analysis showed that: 1) Meticrane induced alteration in the cell viability and proliferation in leukemia cells (Jurkat and K562 cells) and liver cancer (SK-hep-1), however, no evidence of apoptosis was detectable. 2) Meticrane showed additive/synergistic effects with epigenetic inhibitors (DNMT1/5AC, HDACs/CUDC-101 and HDAC6/ACY1215). 3) A genome-wide transcriptional analysis showed that meticrane treatment induces changes in the expression of genes associated with non-cancer associated pathways. Of importance, differentially expressed genes showed favorable correlation with the survival-related genes in the cancer genome. 4) We also performed molecular docking analysis and found considerable binding affinity scores of meticrane against PD-L1, TIM-3, CD73, and HDACs. Additionally, we tested its suitability for immunotherapy against cancers, but meticrane showed no response to the cytotoxicity of cytokine-induced killer (CIK) cells. To our knowledge, our study is the first attempt to identify and experimentally confirm the anti-cancer potential of meticrane, being also the first to test the suitability of any non-oncology drug in CIK cell therapy. Beyond that, we have expressed some concerns confronted during testing meticrane that also apply to other non-oncology drugs when considered for future clinical or preclinical purposes. Taken together, meticrane is involved in some anticancer pathways that are passively targeting cancer cells and may be considered as compatible with epigenetic inhibitors. Frontiers Media S.A. 2023-05-19 /pmc/articles/PMC10235775/ /pubmed/37274234 http://dx.doi.org/10.3389/fonc.2023.1157366 Text en Copyright © 2023 Wang, Sharma, Ge, Chen, Yang, Liu, Liu, Zhao, Mittal, Asthana and Schmidt-Wolf https://creativecommons.org/licenses/by/4.0/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) and the copyright owner(s) 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.
spellingShingle Oncology
Wang, Yulu
Sharma, Amit
Ge, Fangfang
Chen, Peng
Yang, Yu
Liu, Hongjia
Liu, Hongde
Zhao, Chunxia
Mittal, Lovika
Asthana, Shailendra
Schmidt-Wolf, Ingo G. H.
Non-oncology drug (meticrane) shows anti-cancer ability in synergy with epigenetic inhibitors and appears to be involved passively in targeting cancer cells
title Non-oncology drug (meticrane) shows anti-cancer ability in synergy with epigenetic inhibitors and appears to be involved passively in targeting cancer cells
title_full Non-oncology drug (meticrane) shows anti-cancer ability in synergy with epigenetic inhibitors and appears to be involved passively in targeting cancer cells
title_fullStr Non-oncology drug (meticrane) shows anti-cancer ability in synergy with epigenetic inhibitors and appears to be involved passively in targeting cancer cells
title_full_unstemmed Non-oncology drug (meticrane) shows anti-cancer ability in synergy with epigenetic inhibitors and appears to be involved passively in targeting cancer cells
title_short Non-oncology drug (meticrane) shows anti-cancer ability in synergy with epigenetic inhibitors and appears to be involved passively in targeting cancer cells
title_sort non-oncology drug (meticrane) shows anti-cancer ability in synergy with epigenetic inhibitors and appears to be involved passively in targeting cancer cells
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10235775/
https://www.ncbi.nlm.nih.gov/pubmed/37274234
http://dx.doi.org/10.3389/fonc.2023.1157366
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