New Diterpenoids from Mesona procumbens with Antiproliferative Activities Modulate Cell Cycle Arrest and Apoptosis in Human Leukemia Cancer Cells

Mesona procumbens is a popular material used in foods and herbal medicines in Asia for clearing heat and resolving toxins. However, phytochemical research on this plant is very rare. In this study, eleven new diterpenoids, mesonols A-K (1–11), comprising seven &...

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Autores principales:	Hung-Tse Huang, Chia-Ching Liaw, Yu-Chi Lin, Geng-You Liao, Chih-Hua Chao, Chun-Tang Chiou, Yao-Haur Kuo, Kung-Ta Lee
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>Mesona procumbens</i> diterpenoids mesonol apoptosis cell cycle arrest Medicine R Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/f2fa67439164477dabc9974a92c57d5d
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spelling	oai:doaj.org-article:f2fa67439164477dabc9974a92c57d5d2021-11-25T18:39:24ZNew Diterpenoids from <i>Mesona procumbens</i> with Antiproliferative Activities Modulate Cell Cycle Arrest and Apoptosis in Human Leukemia Cancer Cells10.3390/ph141111081424-8247https://doaj.org/article/f2fa67439164477dabc9974a92c57d5d2021-10-01T00:00:00Zhttps://www.mdpi.com/1424-8247/14/11/1108https://doaj.org/toc/1424-8247<i>Mesona procumbens</i> is a popular material used in foods and herbal medicines in Asia for clearing heat and resolving toxins. However, phytochemical research on this plant is very rare. In this study, eleven new diterpenoids, mesonols A-K (<b>1–11</b>), comprising seven <i>ent</i>-kauranes, three <i>ent</i>-atisanes, and one sarcopetalane, were isolated from its methanolic extract. Structural elucidation of compounds <b>1–11</b> was performed by spectroscopic methods, especially 2D NMR, HRESIMS, and X-ray crystallographic analysis. All isolates were assessed for their antiproliferative activity, and compounds <b>1–4</b> showed potential antiproliferative activities against A549, Hep-3B, PC-3, HT29, and U937 cancer cells, with IC<sub>50</sub> values ranging from 1.97 to 19.86 µM. The most active compounds, <b>1</b> and <b>2</b>, were selected for further investigation of their effects on cell cycle progression, apoptosis, and ROS generation in U937 human leukemia cancer cells. Interestingly, it was found that compounds <b>1</b> and <b>2</b> induced antiproliferative effects in U937 cells through different mechanisms. Compound <b>1</b> caused cell cycle arrest at the G2/M phase and subsequent cell death in a dose- and time-dependent manner. However, <b>2</b>-mediated antiproliferation of U937 cells triggered ROS-mediated mitochondrial-dependent apoptosis. These results provide insight into the molecular mechanism involved in the antiproliferative activities of compounds <b>1</b> and <b>2</b> in U937 cells. Altogether, the study showed that new diterpenoid compounds <b>1</b> and <b>2</b> from <i>M. procumbens</i> are potent and promising anticancer agents.Hung-Tse HuangChia-Ching LiawYu-Chi LinGeng-You LiaoChih-Hua ChaoChun-Tang ChiouYao-Haur KuoKung-Ta LeeMDPI AGarticle<i>Mesona procumbens</i>diterpenoidsmesonolapoptosiscell cycle arrestMedicineRPharmacy and materia medicaRS1-441ENPharmaceuticals, Vol 14, Iss 1108, p 1108 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>Mesona procumbens</i> diterpenoids mesonol apoptosis cell cycle arrest Medicine R Pharmacy and materia medica RS1-441
spellingShingle	<i>Mesona procumbens</i> diterpenoids mesonol apoptosis cell cycle arrest Medicine R Pharmacy and materia medica RS1-441 Hung-Tse Huang Chia-Ching Liaw Yu-Chi Lin Geng-You Liao Chih-Hua Chao Chun-Tang Chiou Yao-Haur Kuo Kung-Ta Lee New Diterpenoids from <i>Mesona procumbens</i> with Antiproliferative Activities Modulate Cell Cycle Arrest and Apoptosis in Human Leukemia Cancer Cells
description	<i>Mesona procumbens</i> is a popular material used in foods and herbal medicines in Asia for clearing heat and resolving toxins. However, phytochemical research on this plant is very rare. In this study, eleven new diterpenoids, mesonols A-K (<b>1–11</b>), comprising seven <i>ent</i>-kauranes, three <i>ent</i>-atisanes, and one sarcopetalane, were isolated from its methanolic extract. Structural elucidation of compounds <b>1–11</b> was performed by spectroscopic methods, especially 2D NMR, HRESIMS, and X-ray crystallographic analysis. All isolates were assessed for their antiproliferative activity, and compounds <b>1–4</b> showed potential antiproliferative activities against A549, Hep-3B, PC-3, HT29, and U937 cancer cells, with IC<sub>50</sub> values ranging from 1.97 to 19.86 µM. The most active compounds, <b>1</b> and <b>2</b>, were selected for further investigation of their effects on cell cycle progression, apoptosis, and ROS generation in U937 human leukemia cancer cells. Interestingly, it was found that compounds <b>1</b> and <b>2</b> induced antiproliferative effects in U937 cells through different mechanisms. Compound <b>1</b> caused cell cycle arrest at the G2/M phase and subsequent cell death in a dose- and time-dependent manner. However, <b>2</b>-mediated antiproliferation of U937 cells triggered ROS-mediated mitochondrial-dependent apoptosis. These results provide insight into the molecular mechanism involved in the antiproliferative activities of compounds <b>1</b> and <b>2</b> in U937 cells. Altogether, the study showed that new diterpenoid compounds <b>1</b> and <b>2</b> from <i>M. procumbens</i> are potent and promising anticancer agents.
format	article
author	Hung-Tse Huang Chia-Ching Liaw Yu-Chi Lin Geng-You Liao Chih-Hua Chao Chun-Tang Chiou Yao-Haur Kuo Kung-Ta Lee
author_facet	Hung-Tse Huang Chia-Ching Liaw Yu-Chi Lin Geng-You Liao Chih-Hua Chao Chun-Tang Chiou Yao-Haur Kuo Kung-Ta Lee
author_sort	Hung-Tse Huang
title	New Diterpenoids from <i>Mesona procumbens</i> with Antiproliferative Activities Modulate Cell Cycle Arrest and Apoptosis in Human Leukemia Cancer Cells
title_short	New Diterpenoids from <i>Mesona procumbens</i> with Antiproliferative Activities Modulate Cell Cycle Arrest and Apoptosis in Human Leukemia Cancer Cells
title_full	New Diterpenoids from <i>Mesona procumbens</i> with Antiproliferative Activities Modulate Cell Cycle Arrest and Apoptosis in Human Leukemia Cancer Cells
title_fullStr	New Diterpenoids from <i>Mesona procumbens</i> with Antiproliferative Activities Modulate Cell Cycle Arrest and Apoptosis in Human Leukemia Cancer Cells
title_full_unstemmed	New Diterpenoids from <i>Mesona procumbens</i> with Antiproliferative Activities Modulate Cell Cycle Arrest and Apoptosis in Human Leukemia Cancer Cells
title_sort	new diterpenoids from <i>mesona procumbens</i> with antiproliferative activities modulate cell cycle arrest and apoptosis in human leukemia cancer cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/f2fa67439164477dabc9974a92c57d5d
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New Diterpenoids from <i>Mesona procumbens</i> with Antiproliferative Activities Modulate Cell Cycle Arrest and Apoptosis in Human Leukemia Cancer Cells

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