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Deoxyelephantopin Induces Apoptosis and Enhances Chemosensitivity of Colon Cancer via miR-205/Bcl2 Axis

Colon cancer (CC) is one of the major causes of cancer death in humans. Despite recent advances in the management of CC, the prognosis is still poor and a new strategy for effective therapy is imperative. Deoxyelephantopin (DET), extracted from an important medicinal plant, Elephantopus scaber L., h...

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Autores principales: Ji, Haoyan, Zhang, Kui, Pan, Guangzhao, Li, Changhong, Li, Chongyang, Hu, Xin, Yang, Liqun, Cui, Hongjuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9099879/
https://www.ncbi.nlm.nih.gov/pubmed/35563442
http://dx.doi.org/10.3390/ijms23095051
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author Ji, Haoyan
Zhang, Kui
Pan, Guangzhao
Li, Changhong
Li, Chongyang
Hu, Xin
Yang, Liqun
Cui, Hongjuan
author_facet Ji, Haoyan
Zhang, Kui
Pan, Guangzhao
Li, Changhong
Li, Chongyang
Hu, Xin
Yang, Liqun
Cui, Hongjuan
author_sort Ji, Haoyan
collection PubMed
description Colon cancer (CC) is one of the major causes of cancer death in humans. Despite recent advances in the management of CC, the prognosis is still poor and a new strategy for effective therapy is imperative. Deoxyelephantopin (DET), extracted from an important medicinal plant, Elephantopus scaber L., has been reported to exhibit excellent anti-inflammatory and -cancer activities, while the detailed anti-cancer mechanism remains unclear. Herein, we found that DET showed a significant CC inhibiting effect in vitro and in vivo without obvious organ toxicity. Mechanistically, DET inhibited CC cells and tumor growth by inducing G2/M phase arrest and subsequent apoptosis. DET-mediated cell cycle arrest was caused by severe DNA damage, and DET decreased the Bcl2 expression level in a dose-dependent manner to promote CC cell apoptosis, whereas restoring Bcl2 expression reduced apoptosis to a certain extent. Moreover, we identified a microRNA complementary to the 3′-UTR of Bcl2, miR-205, that responded to the DET treatment. An inhibitor of miR-205 could recover Bcl2 expression and promoted the survival of CC cells upon DET treatment. To further examine the potential value of the drug, we evaluated the combinative effects of DET and 5-Fluorouracil (5FU) through Jin’s formula and revealed that DET acted synergistically with 5FU, resulting in enhancing the chemotherapeutic sensitivity of CC to 5FU. Our results consolidate DET as a potent drug for the treatment of CC when it is used alone or combined with 5FU, and elucidate the importance of the miR-205-Bcl2 axis in DET treatment.
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spelling pubmed-90998792022-05-14 Deoxyelephantopin Induces Apoptosis and Enhances Chemosensitivity of Colon Cancer via miR-205/Bcl2 Axis Ji, Haoyan Zhang, Kui Pan, Guangzhao Li, Changhong Li, Chongyang Hu, Xin Yang, Liqun Cui, Hongjuan Int J Mol Sci Article Colon cancer (CC) is one of the major causes of cancer death in humans. Despite recent advances in the management of CC, the prognosis is still poor and a new strategy for effective therapy is imperative. Deoxyelephantopin (DET), extracted from an important medicinal plant, Elephantopus scaber L., has been reported to exhibit excellent anti-inflammatory and -cancer activities, while the detailed anti-cancer mechanism remains unclear. Herein, we found that DET showed a significant CC inhibiting effect in vitro and in vivo without obvious organ toxicity. Mechanistically, DET inhibited CC cells and tumor growth by inducing G2/M phase arrest and subsequent apoptosis. DET-mediated cell cycle arrest was caused by severe DNA damage, and DET decreased the Bcl2 expression level in a dose-dependent manner to promote CC cell apoptosis, whereas restoring Bcl2 expression reduced apoptosis to a certain extent. Moreover, we identified a microRNA complementary to the 3′-UTR of Bcl2, miR-205, that responded to the DET treatment. An inhibitor of miR-205 could recover Bcl2 expression and promoted the survival of CC cells upon DET treatment. To further examine the potential value of the drug, we evaluated the combinative effects of DET and 5-Fluorouracil (5FU) through Jin’s formula and revealed that DET acted synergistically with 5FU, resulting in enhancing the chemotherapeutic sensitivity of CC to 5FU. Our results consolidate DET as a potent drug for the treatment of CC when it is used alone or combined with 5FU, and elucidate the importance of the miR-205-Bcl2 axis in DET treatment. MDPI 2022-05-02 /pmc/articles/PMC9099879/ /pubmed/35563442 http://dx.doi.org/10.3390/ijms23095051 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
Ji, Haoyan
Zhang, Kui
Pan, Guangzhao
Li, Changhong
Li, Chongyang
Hu, Xin
Yang, Liqun
Cui, Hongjuan
Deoxyelephantopin Induces Apoptosis and Enhances Chemosensitivity of Colon Cancer via miR-205/Bcl2 Axis
title Deoxyelephantopin Induces Apoptosis and Enhances Chemosensitivity of Colon Cancer via miR-205/Bcl2 Axis
title_full Deoxyelephantopin Induces Apoptosis and Enhances Chemosensitivity of Colon Cancer via miR-205/Bcl2 Axis
title_fullStr Deoxyelephantopin Induces Apoptosis and Enhances Chemosensitivity of Colon Cancer via miR-205/Bcl2 Axis
title_full_unstemmed Deoxyelephantopin Induces Apoptosis and Enhances Chemosensitivity of Colon Cancer via miR-205/Bcl2 Axis
title_short Deoxyelephantopin Induces Apoptosis and Enhances Chemosensitivity of Colon Cancer via miR-205/Bcl2 Axis
title_sort deoxyelephantopin induces apoptosis and enhances chemosensitivity of colon cancer via mir-205/bcl2 axis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9099879/
https://www.ncbi.nlm.nih.gov/pubmed/35563442
http://dx.doi.org/10.3390/ijms23095051
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