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Open AccessArticle

Clerodane Diterpene Ameliorates Inflammatory Bowel Disease and Potentiates Cell Apoptosis of Colorectal Cancer

1
Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 97401, Taiwan
2
Department of Orthopedics, Hualien Armed Force General Hospital, Hualien 97144, Taiwan
3
Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei City 11217, Taiwan
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Department of Physiology & Master’s Program, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan
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Department of Food Science & Technology, Tajen University, Pingtung, 90741, Taiwan
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Department of Radiation Oncology, Yeezen Hospital, Taoyuan 32645, Taiwan
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Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
8
Institute of Respiratory Disease, Department of Basic Medical Science, Xiamen Medical College, Xiamen 361023, China
*
Author to whom correspondence should be addressed.
Biomolecules 2019, 9(12), 762; https://doi.org/10.3390/biom9120762
Received: 25 October 2019 / Revised: 20 November 2019 / Accepted: 20 November 2019 / Published: 21 November 2019
(This article belongs to the Special Issue Phytochemical Omics in Medicinal Plants)
Inflammatory bowel disease (IBD) is general term for ulcerative colitis and Crohn’s disease, which is chronic intestinal and colorectal inflammation caused by microbial infiltration or immunocyte attack. IBD is not curable, and is highly susceptible to develop into colorectal cancer. Finding agents to alleviate these symptoms, as well as any progression of IBD, is a critical effort. This study evaluates the anti-inflammation and anti-tumor activity of 16-hydroxycleroda-3,13-dien-15,16-olide (HCD) in in vivo and in vitro assays. The result of an IBD mouse model induced using intraperitoneal chemical azoxymethane (AOM)/dextran sodium sulfate (DSS) injection showed that intraperitoneal HCD adminstration could ameliorate the inflammatory symptoms of IBD mice. In the in vitro assay, cytotoxic characteristics and retained signaling pathways of HCD treatment were analyzed by MTT assay, cell cycle analysis, and Western blotting. From cell viability determination, the IC50 of HCD in Caco-2 was significantly lower in 2.30 μM at 48 h when compared to 5-fluorouracil (5-FU) (66.79 μM). By cell cycle and Western blotting analysis, the cell death characteristics of HCD treatment in Caco-2 exhibited the involvement of extrinsic and intrinsic pathways in cell death, for which intrinsic apoptosis was predominantly activated via the reduction in growth factor signaling. These potential treatments against colon cancer demonstrate that HCD could provide a promising adjuvant as an alternative medicine in combating colorectal cancer and IBD.
Keywords: colorectal cancer; diterpenes; inflammatory bowel diseases; Polyalthia longifolia; herbal medicine. colorectal cancer; diterpenes; inflammatory bowel diseases; Polyalthia longifolia; herbal medicine.
MDPI and ACS Style

Zheng, J.-H.; Lin, S.-R.; Tseng, F.-J.; Tsai, M.-J.; Lue, S.-I.; Chia, Y.-C.; Woon, M.; Fu, Y.-S.; Weng, C.-F. Clerodane Diterpene Ameliorates Inflammatory Bowel Disease and Potentiates Cell Apoptosis of Colorectal Cancer. Biomolecules 2019, 9, 762.

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