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A Combined Treatment with Berberine and Andrographis Exhibits Enhanced Anti-Cancer Activity through Suppression of DNA Replication in Colorectal Cancer

The high morbidity and mortality associated with colorectal cancer (CRC) are largely due to the invariable development of chemoresistance to classic chemotherapies, as well as intolerance to their significant toxicity. Many pharmaceutical formulations screened from natural plant extracts offer safe,...

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Detalles Bibliográficos
Autores principales: Zhao, Yinghui, Roy, Souvick, Wang, Chuanxin, Goel, Ajay
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8953248/
https://www.ncbi.nlm.nih.gov/pubmed/35337060
http://dx.doi.org/10.3390/ph15030262
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author Zhao, Yinghui
Roy, Souvick
Wang, Chuanxin
Goel, Ajay
author_facet Zhao, Yinghui
Roy, Souvick
Wang, Chuanxin
Goel, Ajay
author_sort Zhao, Yinghui
collection PubMed
description The high morbidity and mortality associated with colorectal cancer (CRC) are largely due to the invariable development of chemoresistance to classic chemotherapies, as well as intolerance to their significant toxicity. Many pharmaceutical formulations screened from natural plant extracts offer safe, inexpensive, and multi-target therapeutic options. In this study, we demonstrated that Berberis vulgaris L. (Berberine) and Andrographis paniculata (Burm. f.) Nees (Andrographis) extracts exerted their synergistic amplified anti-cancer effects by jointly inhibiting cell viability, suppressing colony formation, and inducing cell cycle arrest. Consistent with our in-vitro findings, the amplified synergistic anti-cancer effects were also observed in subcutaneous xenograft preclinical animal models, as well as patient-derived primary tumor organoids. To explore the molecular mechanisms underlying the amplified synergistic anti-cancer effects, RNA sequencing was performed to identify candidate pathways and genes. A transcriptome analysis revealed that DNA-replication-related genes, including FEN1, MCM7, PRIM1, MCM5, POLA1, MCM4, and PCNA, may be responsible for the enhanced anticancer effects of these two natural extracts. Taken together, our data revealed the powerful enhanced synergistic anti-CRC effects of berberine and Andrographis and provide evidence for the combinational targeting of DNA-replication-related genes as a promising new strategy for the therapeutic option in the management of CRC patients.
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spelling pubmed-89532482022-03-26 A Combined Treatment with Berberine and Andrographis Exhibits Enhanced Anti-Cancer Activity through Suppression of DNA Replication in Colorectal Cancer Zhao, Yinghui Roy, Souvick Wang, Chuanxin Goel, Ajay Pharmaceuticals (Basel) Article The high morbidity and mortality associated with colorectal cancer (CRC) are largely due to the invariable development of chemoresistance to classic chemotherapies, as well as intolerance to their significant toxicity. Many pharmaceutical formulations screened from natural plant extracts offer safe, inexpensive, and multi-target therapeutic options. In this study, we demonstrated that Berberis vulgaris L. (Berberine) and Andrographis paniculata (Burm. f.) Nees (Andrographis) extracts exerted their synergistic amplified anti-cancer effects by jointly inhibiting cell viability, suppressing colony formation, and inducing cell cycle arrest. Consistent with our in-vitro findings, the amplified synergistic anti-cancer effects were also observed in subcutaneous xenograft preclinical animal models, as well as patient-derived primary tumor organoids. To explore the molecular mechanisms underlying the amplified synergistic anti-cancer effects, RNA sequencing was performed to identify candidate pathways and genes. A transcriptome analysis revealed that DNA-replication-related genes, including FEN1, MCM7, PRIM1, MCM5, POLA1, MCM4, and PCNA, may be responsible for the enhanced anticancer effects of these two natural extracts. Taken together, our data revealed the powerful enhanced synergistic anti-CRC effects of berberine and Andrographis and provide evidence for the combinational targeting of DNA-replication-related genes as a promising new strategy for the therapeutic option in the management of CRC patients. MDPI 2022-02-22 /pmc/articles/PMC8953248/ /pubmed/35337060 http://dx.doi.org/10.3390/ph15030262 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhao, Yinghui
Roy, Souvick
Wang, Chuanxin
Goel, Ajay
A Combined Treatment with Berberine and Andrographis Exhibits Enhanced Anti-Cancer Activity through Suppression of DNA Replication in Colorectal Cancer
title A Combined Treatment with Berberine and Andrographis Exhibits Enhanced Anti-Cancer Activity through Suppression of DNA Replication in Colorectal Cancer
title_full A Combined Treatment with Berberine and Andrographis Exhibits Enhanced Anti-Cancer Activity through Suppression of DNA Replication in Colorectal Cancer
title_fullStr A Combined Treatment with Berberine and Andrographis Exhibits Enhanced Anti-Cancer Activity through Suppression of DNA Replication in Colorectal Cancer
title_full_unstemmed A Combined Treatment with Berberine and Andrographis Exhibits Enhanced Anti-Cancer Activity through Suppression of DNA Replication in Colorectal Cancer
title_short A Combined Treatment with Berberine and Andrographis Exhibits Enhanced Anti-Cancer Activity through Suppression of DNA Replication in Colorectal Cancer
title_sort combined treatment with berberine and andrographis exhibits enhanced anti-cancer activity through suppression of dna replication in colorectal cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8953248/
https://www.ncbi.nlm.nih.gov/pubmed/35337060
http://dx.doi.org/10.3390/ph15030262
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