Acorus gramineus extract decreases cancer stem cell properties and stimulates ROS signaling pathway in HepG2 hepatocellular carcinoma cells

ABTRACT: Background: Acorus gramineus is called “Shi Chang Pu'” in Chinese and has been used in traditional Chinese medicine (TCM) for over 2,000 years. The records in the 'Shennong Bencao Jing' show that many species in the genus Acorus are used to treat various diseases in humans s...

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Main Authors: Van Hung Hoang, Thi Thanh Huong Le, Phu Hung Nguyen, Viet Hoang, Van Khang Pham, Thi Kieu Oanh Nguyen, Dinh Quang Hung Can
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Pharmacological Research - Modern Chinese Medicine
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Online Access:http://www.sciencedirect.com/science/article/pii/S2667142524001908
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author Van Hung Hoang
Thi Thanh Huong Le
Phu Hung Nguyen
Viet Hoang
Van Khang Pham
Thi Kieu Oanh Nguyen
Dinh Quang Hung Can
author_facet Van Hung Hoang
Thi Thanh Huong Le
Phu Hung Nguyen
Viet Hoang
Van Khang Pham
Thi Kieu Oanh Nguyen
Dinh Quang Hung Can
author_sort Van Hung Hoang
collection DOAJ
description ABTRACT: Background: Acorus gramineus is called “Shi Chang Pu'” in Chinese and has been used in traditional Chinese medicine (TCM) for over 2,000 years. The records in the 'Shennong Bencao Jing' show that many species in the genus Acorus are used to treat various diseases in humans such as epilepsy, cardiovascular issues, abdominal pain, memory loss, etc. Several species of the genus Acorus have been demonstrated to exhibit antiproliferative effects against various cancer cell lines. This study aims to evaluate the inhitory effects of Acorus gramineus extract (AGE) on HepG2 liver cancer cells. Methods: The inhibitory effect of AGE on HepG2 cell proliferation was assessed using the MTT assay. Migration was analyzed using the wound healing technique. The 3D culture technique was employed to evaluate tumorsphere formation and the invasive potential of cancer cells. Real-time PCR was used for mRNA expression analysis. Changes in the expression levels of CD44 protein and ROS were analyzed using fluorescence staining techniques. Chemical compounds of AGE were identified using UPLC-QToF-MS. Results: The results indicate that AGE exhibits potent inhibitory activity against cell proliferation, with an IC50 value of 34.1 mg/mL. AGE significantly inhibited both the formation and growth of tumorspheres in 3D cultures, reducing both their number and size. Additionally, AGE was found to suppress the invassion of cancer cells. AGE regulated the downregulation of stem cell-related markers including NANOG, SOX2, OCT4, and ALDH. AGE was also shown to increase the production of reactive oxygen species (ROS) within cells by activating genes involved in ROS signaling pathways, which may lead to a decrease in cell proliferation, migration, and invasion, as well as a reduction in cancer stem cell properties. Finally, 58 compounds present in AGE were identified by UPLC-QtoF-MS analysis, and Mulberrofuran K, Akebonoic acid, and Shancilin were evaluated for their affinity with protein markers related to liver cancer stem cells. Conclusion: This study is the first report on the inhibitory activity of AGE against cancer stem cell characteristics in HepG2 cells, highlighting the potential of this plant species as an anti-liver cancer agent.
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series Pharmacological Research - Modern Chinese Medicine
spelling doaj-art-6164cf8f21984f5da09c7c79f0ab28282024-12-19T11:02:27ZengElsevierPharmacological Research - Modern Chinese Medicine2667-14252024-12-0113100548Acorus gramineus extract decreases cancer stem cell properties and stimulates ROS signaling pathway in HepG2 hepatocellular carcinoma cellsVan Hung Hoang0Thi Thanh Huong Le1Phu Hung Nguyen2Viet Hoang3Van Khang Pham4Thi Kieu Oanh Nguyen5Dinh Quang Hung Can6Thai Nguyen University (TNU), Thai Nguyen City, VietnamFaculty of Biotechnology, TNU- University of Sciences (TNUS), Thai Nguyen City, VietnamThai Nguyen University (TNU), Thai Nguyen City, Vietnam; Corresonding author.Faculty of Biotechnology, TNU- University of Sciences (TNUS), Thai Nguyen City, VietnamFaculty of Chemistry, TNU – University of Education (TNUE), Thai Nguyen City, VietnamUniversity of Science and Technology of Hanoi, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Ha Noi, VietnamFaculty of Biotechnology, TNU- University of Sciences (TNUS), Thai Nguyen City, VietnamABTRACT: Background: Acorus gramineus is called “Shi Chang Pu'” in Chinese and has been used in traditional Chinese medicine (TCM) for over 2,000 years. The records in the 'Shennong Bencao Jing' show that many species in the genus Acorus are used to treat various diseases in humans such as epilepsy, cardiovascular issues, abdominal pain, memory loss, etc. Several species of the genus Acorus have been demonstrated to exhibit antiproliferative effects against various cancer cell lines. This study aims to evaluate the inhitory effects of Acorus gramineus extract (AGE) on HepG2 liver cancer cells. Methods: The inhibitory effect of AGE on HepG2 cell proliferation was assessed using the MTT assay. Migration was analyzed using the wound healing technique. The 3D culture technique was employed to evaluate tumorsphere formation and the invasive potential of cancer cells. Real-time PCR was used for mRNA expression analysis. Changes in the expression levels of CD44 protein and ROS were analyzed using fluorescence staining techniques. Chemical compounds of AGE were identified using UPLC-QToF-MS. Results: The results indicate that AGE exhibits potent inhibitory activity against cell proliferation, with an IC50 value of 34.1 mg/mL. AGE significantly inhibited both the formation and growth of tumorspheres in 3D cultures, reducing both their number and size. Additionally, AGE was found to suppress the invassion of cancer cells. AGE regulated the downregulation of stem cell-related markers including NANOG, SOX2, OCT4, and ALDH. AGE was also shown to increase the production of reactive oxygen species (ROS) within cells by activating genes involved in ROS signaling pathways, which may lead to a decrease in cell proliferation, migration, and invasion, as well as a reduction in cancer stem cell properties. Finally, 58 compounds present in AGE were identified by UPLC-QtoF-MS analysis, and Mulberrofuran K, Akebonoic acid, and Shancilin were evaluated for their affinity with protein markers related to liver cancer stem cells. Conclusion: This study is the first report on the inhibitory activity of AGE against cancer stem cell characteristics in HepG2 cells, highlighting the potential of this plant species as an anti-liver cancer agent.http://www.sciencedirect.com/science/article/pii/S2667142524001908Liver cancer cellsROS signalingCancer stem cellsCD44 markertumorsphere
spellingShingle Van Hung Hoang
Thi Thanh Huong Le
Phu Hung Nguyen
Viet Hoang
Van Khang Pham
Thi Kieu Oanh Nguyen
Dinh Quang Hung Can
Acorus gramineus extract decreases cancer stem cell properties and stimulates ROS signaling pathway in HepG2 hepatocellular carcinoma cells
Pharmacological Research - Modern Chinese Medicine
Liver cancer cells
ROS signaling
Cancer stem cells
CD44 marker
tumorsphere
title Acorus gramineus extract decreases cancer stem cell properties and stimulates ROS signaling pathway in HepG2 hepatocellular carcinoma cells
title_full Acorus gramineus extract decreases cancer stem cell properties and stimulates ROS signaling pathway in HepG2 hepatocellular carcinoma cells
title_fullStr Acorus gramineus extract decreases cancer stem cell properties and stimulates ROS signaling pathway in HepG2 hepatocellular carcinoma cells
title_full_unstemmed Acorus gramineus extract decreases cancer stem cell properties and stimulates ROS signaling pathway in HepG2 hepatocellular carcinoma cells
title_short Acorus gramineus extract decreases cancer stem cell properties and stimulates ROS signaling pathway in HepG2 hepatocellular carcinoma cells
title_sort acorus gramineus extract decreases cancer stem cell properties and stimulates ros signaling pathway in hepg2 hepatocellular carcinoma cells
topic Liver cancer cells
ROS signaling
Cancer stem cells
CD44 marker
tumorsphere
url http://www.sciencedirect.com/science/article/pii/S2667142524001908
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