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Kim S, Lee YK, Lee WJ, Jong Moon H, Lee S. Rhus Verniciflua Stokes Inhibits PD-1 Expression and Induces Anticancer Effects by Enhancing T Cell Function. Integr Cancer Ther 2025; 24:15347354241308220. [PMID: 39760460 PMCID: PMC11705362 DOI: 10.1177/15347354241308220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Revised: 10/19/2024] [Accepted: 12/04/2024] [Indexed: 01/07/2025] Open
Abstract
BACKGROUND Over the last decade, the anticancer effects of Rhus verniciflua Stokes (RVS) have been reported in various preclinical or clinical studies. However, the effects of RVS on immuno-oncology, especially on the functional properties of T cells and their phenotypes, remain unclear. Here, we planned to investigate the impact of RVS on immuno-oncology, specifically focusing on its effects on T cells. METHODS Peripheral blood mononuclear cells (PBMCs) from breast cancer patients were isolated to obtain cytokine-induced killer cell populations with >85% CD3+ T cells. The anticancer activity of these T cells was evaluated by introducing red fluorescent protein (RFP) into HLA-A02:01 type-matched breast cancer cell lines (MCF7 and MDA-MB-231) and analyzing the results using flow cytometry. The effect of RVS extracts on T cell phenotype was assessed using markers such as CTLA-4 and PD-1, as well as mRNA expression levels of key genes (IFN-γ, TNF-α, and IL-2). RESULTS RVS treatment significantly enhanced the anticancer activity of T cells against breast cancer cells. Specifically, T cells treated with 100 µg/mL of RVS showed a 20.6% increase in cytotoxicity against MCF-7 cells and a 36.2% increase against MDA-MB231 cells compared to the control. Additionally, RVS treatment led to a significant reduction in PD-1 expression on T cells. CONCLUSION Our findings demonstrate that RVS treatment enhances T cell function against breast cancer cells by reducing PD-1 expression. These results suggest that components of RVS may serve as potential candidates for restoring exhausted T cells in cancer therapy.
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Affiliation(s)
- Seoyoung Kim
- Eutilex Co. Ltd., Geumcheon-gu, Seoul, Republic of Korea
| | - Young-Kwan Lee
- Excelsisbio Inc., Goyang-si, Gyeonggi-do, Republic of Korea
| | - Wang-Jun Lee
- Myongji Hospital, Goyang-si, Gyeonggi-do, Republic of Korea
| | | | - Sanghun Lee
- Myongji Hospital, Goyang-si, Gyeonggi-do, Republic of Korea
- Department of Bioconvergence & Engineering, Dankook University, Yongin-si, Gyeonggi-do, Republic of Korea
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Frenț OD, Stefan L, Morgovan CM, Duteanu N, Dejeu IL, Marian E, Vicaș L, Manole F. A Systematic Review: Quercetin-Secondary Metabolite of the Flavonol Class, with Multiple Health Benefits and Low Bioavailability. Int J Mol Sci 2024; 25:12091. [PMID: 39596162 PMCID: PMC11594109 DOI: 10.3390/ijms252212091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Revised: 11/01/2024] [Accepted: 11/06/2024] [Indexed: 11/28/2024] Open
Abstract
The main goal of this systematic review on the flavonol class secondary metabolite quercetin is to evaluate and summarize the existing research on quercetin's potential health benefits, therapeutic properties, and effectiveness in disease prevention and treatment. In addition to evaluating quercetin's potential for drug development with fewer side effects and lower toxicity, this type of review attempts to collect scientific evidence addressing quercetin's roles as an antioxidant, anti-inflammatory, antibacterial, and anticancer agent. In the first part, we analyze various flavonoid compounds, focusing on their chemical structure, classification, and natural sources. We highlight their most recent biological activities as reported in the literature. Among these compounds, we pay special attention to quercetin, detailing its chemical structure, physicochemical properties, and process of biosynthesis in plants. We also present natural sources of quercetin and emphasize its health benefits, such as its antioxidant and anti-inflammatory effects. Additionally, we discuss methods to enhance its bioavailability, analyzing the latest and most effective delivery systems based on quercetin.
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Affiliation(s)
- Olimpia-Daniela Frenț
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, No. 29 Nicolae Jiga Street, 410028 Oradea, Romania; (O.-D.F.); (E.M.); (L.V.)
| | - Liana Stefan
- Department of Surgical Discipline, Faculty of Medicine and Pharmacy, University of Oradea, 410087 Oradea, Romania
| | - Claudia Mona Morgovan
- Department of Chemistry, Faculty of Informatics and Sciences, University of Oradea, No 1 University Street, 410087 Oradea, Romania
| | - Narcis Duteanu
- Faculty of Chemical Engineering, Biotechnologies, and Environmental Protection, Politehnica University of Timisoara, No. 2 Victoriei Square, 300006 Timişoara, Romania
- National Institute of Research and Development for Electrochemistry and Condensed Matter, 144 Dr. A. P. Podeanu, 300569 Timisoara, Romania
| | - Ioana Lavinia Dejeu
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, No. 29 Nicolae Jiga Street, 410028 Oradea, Romania; (O.-D.F.); (E.M.); (L.V.)
| | - Eleonora Marian
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, No. 29 Nicolae Jiga Street, 410028 Oradea, Romania; (O.-D.F.); (E.M.); (L.V.)
| | - Laura Vicaș
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, No. 29 Nicolae Jiga Street, 410028 Oradea, Romania; (O.-D.F.); (E.M.); (L.V.)
| | - Felicia Manole
- Department of Surgical Discipline, Faculty of Medicine and Pharmacy, University of Oradea, 410087 Oradea, Romania
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Mazumder R, Ichudaule, Ghosh A, Deb S, Ghosh R. Significance of Chalcone Scaffolds in Medicinal Chemistry. Top Curr Chem (Cham) 2024; 382:22. [PMID: 38937401 DOI: 10.1007/s41061-024-00468-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Accepted: 05/24/2024] [Indexed: 06/29/2024]
Abstract
Chalcone is a simple naturally occurring α,β-unsaturated ketone with biological importance, which can also be easily synthesized in laboratories by reaction between two aromatic scaffolds. In plants, chalcones occur as polyphenolic compounds of different frameworks which are bioactive molecules that have been in traditional medicinal practice for many years. Chalcone-based lead molecules have been developed, possessing varied potentials such as antimicrobial, antiviral, anti-inflammatory, anticancer, anti-oxidant, antidiabetic, antihyperurecemic, and anti-ulcer effects. Chalcones contribute considerable fragments to give important heterocyclic molecules with therapeutic utilities targeting various diseases. These characteristic features have made chalcone a topic of interest among researchers and have attracted investigations into this widely applicable structure. This review highlights the extensive exploration carried out on the synthesis, biotransformations, chemical reactions, hybridization, and pharmacological potentials of chalcones, and aims to provide an extensive, thorough, and critical review of their importance, with emphasis on their properties, chemistry, and biomedical applications to boost future investigations into this potential scaffold in medicinal chemistry.
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Affiliation(s)
- Rishav Mazumder
- Laboratory of Developing Drug Candidates, Department of Pharmacy, Tripura University (A Central University), Suryamaninagar, Agartala, Tripura, 799022, India
| | - Ichudaule
- Laboratory of Developing Drug Candidates, Department of Pharmacy, Tripura University (A Central University), Suryamaninagar, Agartala, Tripura, 799022, India
| | - Ashmita Ghosh
- Department of Microbiology and Biotechnology, School of Natural Sciences, Techno India University Tripura, Maheshkhola, Anandanagar, Agartala, Tripura, 799004, India
| | - Subrata Deb
- Department of Pharmaceutical Sciences, College of Pharmacy, Larkin University, Miami, FL, 33169, USA.
| | - Rajat Ghosh
- Laboratory of Developing Drug Candidates, Department of Pharmacy, Tripura University (A Central University), Suryamaninagar, Agartala, Tripura, 799022, India.
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Hu X, Wang M, Cai F, Liu L, Cheng Z, Zhao J, Zhang Q, Long C. A comprehensive review of medicinal Toxicodendron (Anacardiaceae): Botany, traditional uses, phytochemistry and pharmacology. JOURNAL OF ETHNOPHARMACOLOGY 2024; 318:116829. [PMID: 37429501 DOI: 10.1016/j.jep.2023.116829] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Revised: 06/03/2023] [Accepted: 06/20/2023] [Indexed: 07/12/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Comprising of about 30 species, the genus Toxicodendron (Anacardiaceae) are mainly distributed in East Asia and North America. Among them, 13 species have been traditionally used as folk medicines in Asia and other parts of the world to treat blood diseases, abnormal bleeding, skin diseases, gastrointestinal diseases, liver diseases, bone injury, lung diseases, neurological diseases, cardiovascular diseases, tonic, cancer, eye diseases, menstrual irregularities, inflammation, rheumatism, diabetes mellitus, rattlesnake bite, internal parasites, contraceptive, vomiting and diarrhea. AIM OF THE STUDY To date, no comprehensive review on Toxicodendron has been published and the scientific basis of the traditional medicinal benefits of Toxicodendron have been less reported. Therefore, this review aims to provide a reference for further research and development on medicinal purpose of Toxicodendron by summarizing the works (from 1980 to 2023), and focusing on its botany, traditional uses, phytochemistry and pharmacology. MATERIALS AND METHODS The names of the species were from The Plant List Database (http://www.theplantlist.org), World Flora Online (http://www.worldfloraonline.org), Catalogue of Life Database (https://www.catalogueoflife.org/) and Plants for A Future Database (https://pfaf.org/user/Default.aspx). And the search terms "Toxicodendron" and "the names of 31 species and their synonyms" were used to search for information from electronic databases such as Web of Science, Scopus, Google Scholar, Science Direct, PubMed, Baidu Scholar, Springer, and Wiley Online Library. Moreover, PhD and MSc dissertations were also used to support this work. RESULTS These species on Toxicodendron are widely used in folkloric medicine and modern pharmacological activities. So far, approximately 238 compounds, mainly phenolic acids and their derivatives, urushiols, flavonoids and terpenoids, are extracted and isolated from Toxicodendron plants, commonly, T. trichocarpum, T. vernicifluum, T. succedaneum, and T. radicans. Among them, phenolic acids and flavonoids are the main compound classes that show pharmacological activities in Toxicodendron plants both in vitro and in vivo. Furthermore, the extracts and single compounds of these species show a wide range of activities, such as antioxidant, antibacterial, anti-inflammatory, anti-tumor, liver protection, fat reduction, nerve protection, and treatment of blood diseases. CONCLUSIONS Selected species of Toxicodendron have been used as herbal medicines in the Southeast Asian for a long time. Furthermore, some bioactive constituents have been identified from them, so plants in this genus may be potential new drugs. The existing research on Toxicodendron has been reviewed, and the phytochemistry and pharmacology provide theoretical basis for some of the traditional medicinal uses. Therefore, in this review, the traditional medicinal, phytochemical and modern pharmacology of Toxicodendron plants are summarized to help future researchers to find new drug leads or to get a better understanding of structure-activity relationships.
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Affiliation(s)
- Xian Hu
- Key Laboratory of Ecology and Environment in Minority Areas (Minzu University of China), National Ethnic Affairs Commission, Beijing, 100081, China; College of Ethnology and Sociology, Minzu University of China, Beijing, 100081, China; College of Life and Environmental Sciences, Minzu University of China, Beijing, 100081, China; Key Laboratory of Ethnomedicine (Minzu University of China), Ministry of Education, Beijing, 100081, China
| | - Miaomiao Wang
- Key Laboratory of Ecology and Environment in Minority Areas (Minzu University of China), National Ethnic Affairs Commission, Beijing, 100081, China; College of Life and Environmental Sciences, Minzu University of China, Beijing, 100081, China; Key Laboratory of Ethnomedicine (Minzu University of China), Ministry of Education, Beijing, 100081, China
| | - Fei Cai
- Key Laboratory of Ecology and Environment in Minority Areas (Minzu University of China), National Ethnic Affairs Commission, Beijing, 100081, China; College of Life and Environmental Sciences, Minzu University of China, Beijing, 100081, China
| | - Liya Liu
- Key Laboratory of Ecology and Environment in Minority Areas (Minzu University of China), National Ethnic Affairs Commission, Beijing, 100081, China; College of Life and Environmental Sciences, Minzu University of China, Beijing, 100081, China; Key Laboratory of Ethnomedicine (Minzu University of China), Ministry of Education, Beijing, 100081, China
| | - Zhuo Cheng
- Key Laboratory of Ecology and Environment in Minority Areas (Minzu University of China), National Ethnic Affairs Commission, Beijing, 100081, China; College of Life and Environmental Sciences, Minzu University of China, Beijing, 100081, China; Key Laboratory of Ethnomedicine (Minzu University of China), Ministry of Education, Beijing, 100081, China
| | - Jiaqi Zhao
- Key Laboratory of Ecology and Environment in Minority Areas (Minzu University of China), National Ethnic Affairs Commission, Beijing, 100081, China; College of Ethnology and Sociology, Minzu University of China, Beijing, 100081, China; Key Laboratory of Ethnomedicine (Minzu University of China), Ministry of Education, Beijing, 100081, China
| | - Qing Zhang
- Key Laboratory of Ecology and Environment in Minority Areas (Minzu University of China), National Ethnic Affairs Commission, Beijing, 100081, China; College of Life and Environmental Sciences, Minzu University of China, Beijing, 100081, China; Key Laboratory of Ethnomedicine (Minzu University of China), Ministry of Education, Beijing, 100081, China
| | - Chunlin Long
- Key Laboratory of Ecology and Environment in Minority Areas (Minzu University of China), National Ethnic Affairs Commission, Beijing, 100081, China; College of Life and Environmental Sciences, Minzu University of China, Beijing, 100081, China; Key Laboratory of Ethnomedicine (Minzu University of China), Ministry of Education, Beijing, 100081, China; Mass Spectrometry Imaging and Metabolomics (Minzu University of China), National Ethnic Affairs Commission, Beijing, 100081, China; Institute of National Security Studies, Minzu University of China, Beijing, 100081, China.
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Michalkova R, Mirossay L, Kello M, Mojzisova G, Baloghova J, Podracka A, Mojzis J. Anticancer Potential of Natural Chalcones: In Vitro and In Vivo Evidence. Int J Mol Sci 2023; 24:10354. [PMID: 37373500 DOI: 10.3390/ijms241210354] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Revised: 06/12/2023] [Accepted: 06/17/2023] [Indexed: 06/29/2023] Open
Abstract
There is no doubt that significant progress has been made in tumor therapy in the past decades. However, the discovery of new molecules with potential antitumor properties still remains one of the most significant challenges in the field of anticancer therapy. Nature, especially plants, is a rich source of phytochemicals with pleiotropic biological activities. Among a plethora of phytochemicals, chalcones, the bioprecursors of flavonoid and isoflavonoids synthesis in higher plants, have attracted attention due to the broad spectrum of biological activities with potential clinical applications. Regarding the antiproliferative and anticancer effects of chalcones, multiple mechanisms of action including cell cycle arrest, induction of different forms of cell death and modulation of various signaling pathways have been documented. This review summarizes current knowledge related to mechanisms of antiproliferative and anticancer effects of natural chalcones in different types of malignancies including breast cancers, cancers of the gastrointestinal tract, lung cancers, renal and bladder cancers, and melanoma.
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Affiliation(s)
- Radka Michalkova
- Department of Pharmacology, Faculty of Medicine, Pavol Jozef Šafárik University, 040 01 Košice, Slovakia
| | - Ladislav Mirossay
- Department of Pharmacology, Faculty of Medicine, Pavol Jozef Šafárik University, 040 01 Košice, Slovakia
| | - Martin Kello
- Department of Pharmacology, Faculty of Medicine, Pavol Jozef Šafárik University, 040 01 Košice, Slovakia
| | - Gabriela Mojzisova
- Center of Clinical and Preclinical Research MEDIPARK, Faculty of Medicine, Pavol Jozef Šafárik University, 040 01 Košice, Slovakia
| | - Janette Baloghova
- Department of Dermatovenerology, Faculty of Medicine, Pavol Jozef Šafárik University, 040 01 Košice, Slovakia
| | - Anna Podracka
- Department of Dermatovenerology, Faculty of Medicine, Pavol Jozef Šafárik University, 040 01 Košice, Slovakia
| | - Jan Mojzis
- Department of Pharmacology, Faculty of Medicine, Pavol Jozef Šafárik University, 040 01 Košice, Slovakia
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Aidhen IS, Srikanth S, Lal H. The Emerging Promise with O/C‐Glycosides of Important Dietary Phenolic Compounds. European J Org Chem 2022. [DOI: 10.1002/ejoc.202200758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Affiliation(s)
- Indrapal Singh Aidhen
- Indian Institute of Technology Madras Department of Chemistry Adyar 600036 Chennai INDIA
| | | | - Heera Lal
- Indian Institute of Technology Madras Chemistry 600036 Chennai INDIA
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Milosavljevic S, Djordjevic I, Mandic B, Tesevic V, Stankovic M, Todorovic N, Novakovic M. Flavonoids of the Heartwood of Cotinus coggygria Scop. Showing Protective Effect on Human Lymphocyte DNA. Nat Prod Commun 2021. [DOI: 10.1177/1934578x211067289] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
In continuation of our study on Cotinus coggygria from Serbia, 10 known flavonoids (1-10) were isolated from the methylene chloride/methanol extract of the heartwood. They were tested for in vitro protective effect against chromosome aberrations in peripheral human lymphocytes, using the cytokinesis-block micronucleus assay. All tested compounds (in minimal doses of 1 μg/mL) exerted a beneficial effect by decreasing DNA damage of human lymphocytes in the range of 24.2% to 54.5%, better than the radio protectant control, amifostine. Functional groups, such as 3′,4′-dihydroxyphenyl (catechol), 5-OH, 3-OH, and 4-keto in flavonoids (3-keto in aurones), which play a key role in antioxidant activity, are proposed to be responsible for the DNA protective activity of the tested compounds.
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Affiliation(s)
| | - Iris Djordjevic
- Faculty of Veterinary Medicine, University of Belgrade, Belgrade, Serbia
| | - Boris Mandic
- Faculty of Chemistry, University of Belgrade, Belgrade, Serbia
| | - Vele Tesevic
- Faculty of Chemistry, University of Belgrade, Belgrade, Serbia
| | | | - Nina Todorovic
- Instituite of Chemistry, Technology and Metallurgy, Department of Chemistry, University of Belgrade, Belgrade, Serbia
| | - Miroslav Novakovic
- Faculty of Veterinary Medicine, University of Belgrade, Belgrade, Serbia
- Dedicated to Professor Yoshinori Asakawa on the occasion of his 80th birthday
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Rampogu S, Kim SM, Shaik B, Lee G, Kim JH, Kim GS, Lee KW, Kim MO. Novel Butein Derivatives Repress DDX3 Expression by Inhibiting PI3K/AKT Signaling Pathway in MCF-7 and MDA-MB-231 Cell Lines. Front Oncol 2021; 11:712824. [PMID: 34485148 PMCID: PMC8416463 DOI: 10.3389/fonc.2021.712824] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Accepted: 06/10/2021] [Indexed: 11/30/2022] Open
Abstract
Background Breast cancer is one of the major causes of mortalities noticed in women globally. DDX3 has emerged as a potent target for several cancers, including breast cancer to which currently there are no reported or approved drugs. Methods To find effective cancer therapeutics, three compounds were computationally designed tweaking the structure of natural compound butein. These compounds were synthesized and evaluated for their anticancer property in MCF-7 and MDA-MB-231 cell lines targeting DDX3. The in silico molecular docking studies have shown that the compounds have occupied the binding site of the human DDX3 target. Furthermore, to investigate the cell viability effect of 3a, 3b, and 3c on MCF-7 and MDA-MB-231 cell lines, the cell lines were treated with different concentrations of compounds for 24 and 48 h and measured using MTT assay. Results The cell viability results showed that the have induced dose dependent suppression of DDX3 expression. Additionally, 3b and 3c have reduced the expression of DDX3 in MCF-7 and MDA-MD-231 cell lines. 3b or 3c treated cell lines increased apoptotic protein expression. Both the compounds have induced the apoptotic cell death by elevated levels of cleaved PARP and cleaved caspase 3 and repression of the anti-apoptosis protein BCL-xL. Additionally, they have demonstrated the G2/M phase cell cycle arrest in both the cell lines. Additionally, 3c decreased PI3K and AKT levels. Conclusions Our results shed light on the anticancer ability of the designed compounds. These compounds can be employed as chemical spaces to design new prospective drug candidates. Additionally, our computational method can be adapted to design new chemical scaffolds as plausible inhibitors.
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Affiliation(s)
- Shailima Rampogu
- Division of Life Sciences, Division of Applied Life Science (BK21 Plus), Research Institute of Natural Science (RINS), Gyeongsang National University (GNU), Jinju, South Korea.,Division of Life Science and Applied Life Science (BK 21 Plus), College of Natural Sciences, Gyeongsang National University, Jinju, South Korea
| | - Seong Min Kim
- Research Institute of Life Science and College of Veterinary Medicine, Gyeongsang National University, Jinju, South Korea
| | - Baji Shaik
- Department of Chemistry (BK 21 Plus), Research Institute of Natural Science (RINS), Gyeongsang National University, Jinju, South Korea
| | - Gihwan Lee
- Division of Life Sciences, Division of Applied Life Science (BK21 Plus), Research Institute of Natural Science (RINS), Gyeongsang National University (GNU), Jinju, South Korea
| | - Ju Hyun Kim
- Department of Chemistry (BK 21 Plus), Research Institute of Natural Science (RINS), Gyeongsang National University, Jinju, South Korea
| | - Gon Sup Kim
- Research Institute of Life Science and College of Veterinary Medicine, Gyeongsang National University, Jinju, South Korea
| | - Keun Woo Lee
- Division of Life Sciences, Division of Applied Life Science (BK21 Plus), Research Institute of Natural Science (RINS), Gyeongsang National University (GNU), Jinju, South Korea
| | - Myeong Ok Kim
- Division of Life Science and Applied Life Science (BK 21 Plus), College of Natural Sciences, Gyeongsang National University, Jinju, South Korea
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Lee HS, Jung JI, Kim KH, Park SJ, Kim EJ. Rhus verniciflua Stokes extract suppresses migration and invasion in human gastric adenocarcinoma AGS cells. Nutr Res Pract 2020; 14:463-477. [PMID: 33029287 PMCID: PMC7520559 DOI: 10.4162/nrp.2020.14.5.463] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Revised: 03/27/2020] [Accepted: 05/20/2020] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND/OBJECTIVES Many studies have suggested that Rhus verniciflua Stokes (RVS) and its extract are anticancer agents. However, RVS had limited use because it contains urushiol, an allergenic toxin. By improving an existing allergen-removal extraction method, we developed a new allergen-free Rhus verniciflua Stokes extract (RVSE) with higher flavonoid content. In this study, we examined whether RVSE inhibits the ability of AGS gastric cancer cells to migrate and invade. MATERIALS/METHODS The flavonoids content of RVSE was analyzed by HPLC. The effects of RVSE on migration and invasion in AGS cells were analyzed by each assay kit. Matrix metalloproteinase (MMP)-9, plasminogen activator inhibitor-1 (PAI-1) and urokinase-type plasminogen activator (uPA) protein expression was analyzed by protein antibody array. The Phosphorylation of signal transducer and activator of transcription (STAT) 3 were assayed by Western blot analysis. RESULTS RVSE treatment with 0-100 μg/mL dose-dependently reduced the ability of AGS cells to migrate and invade. Notably, treatment with RVSE strongly inhibited the expression of MMP-9 and uPA and the phosphorylation of STAT3. In contrast, RVSE treatment dramatically increased the expression of PAI-1. These results indicate that the inhibition of MMP-9 and uPA expression and STAT3 phosphorylation and the stimulation of PAI-1 expression contributed to the decreased migration and invasion of AGS cells treated with RVSE. CONCLUSIONS These results suggest that RVSE may be used as a natural herbal agent to reduce gastric cancer metastasis.
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Affiliation(s)
- Hyun Sook Lee
- Department of Food Science & Nutrition, Dongseo University, Busan 47011, Korea
| | - Jae In Jung
- Regional Strategic Industry Innovation Center, Hallym University, Chuncheon 24252, Korea
| | | | | | - Eun Ji Kim
- Regional Strategic Industry Innovation Center, Hallym University, Chuncheon 24252, Korea
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Comparison of solubility enhancement by solid dispersion and micronized butein and its correlation with in vivo study. JOURNAL OF PHARMACEUTICAL INVESTIGATION 2020. [DOI: 10.1007/s40005-020-00486-9] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Butein Promotes Lineage Commitment of Bone Marrow-Derived Stem Cells into Osteoblasts via Modulating ERK1/2 Signaling Pathways. Molecules 2020; 25:molecules25081885. [PMID: 32325749 PMCID: PMC7221720 DOI: 10.3390/molecules25081885] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Revised: 04/13/2020] [Accepted: 04/17/2020] [Indexed: 01/16/2023] Open
Abstract
Butein is a phytochemical that belongs to the chalcone family of flavonoids and has antitumor, anti-inflammatory, and anti-osteoclastic bone resorption activities. This study aims to investigate the effects of butein on the differentiation potential of mouse primary bone marrow-derived mesenchymal stem cells (mBMSCs) into osteoblast and adipocyte lineages. Primary cultures of mBMSCs are treated with different doses of butein during its differentiation. Osteoblast differentiation is assessed by alkaline phosphatase (ALP) activity quantification and Alizarin red staining for matrix mineralization, while adipogenesis is assessed by quantification of lipid accumulation using Oil Red O staining. Osteoblastic and adipocytic gene expression markers are determined by quantitative real-time PCR (qPCR). Western blot analysis is used to study the activation of extracellular signal-regulated kinase (ERK1/2). Interestingly, butein promotes the lineage commitment of mBMSCs into osteoblasts, while suppressing their differentiation into adipocytes in a dose-dependent manner. A similar effect of butein is confirmed in human (h) primary BMSCs. Occurring at the molecular level, butein significantly upregulates the mRNA expression of osteoblast-related genes, while downregulating the expression of adipocyte-related genes. The mechanism of butein-induced osteogenesis is found to be mediated by activating the ERK1/2 signaling pathway. To conclude, we identify butein as a novel nutraceutical compound with an osteo-anabolic activity to promote the lineage commitment of BMSCs into osteoblast versus adipocyte. Thus, butein can be a plausible therapeutic drug for enhancing bone formation in osteoporotic patients.
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Ravi M, Sneka MK, Joshipura A. The culture conditions and outputs from breast cancer cell line in vitro experiments. Exp Cell Res 2019; 383:111548. [PMID: 31398351 DOI: 10.1016/j.yexcr.2019.111548] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2019] [Revised: 08/02/2019] [Accepted: 08/03/2019] [Indexed: 10/26/2022]
Abstract
One of the major cancer types that have gained significant importance globally is the breast cancer due to its socio-economic impact. Breast cancer research is an area of considerable importance and several types of material are available for research applications. These include cancer cell lines which can be utilized in several ways. Cell lines are convenient to use and recently about 84 human breast cancer cell lines were classified by molecular sub-typing. These cells lines come under five major molecular subtypes namely the luminal A and B, HER-2+, triple- A and B subtypes. These cell lines have been well characterized and were utilized for understanding various aspects of breast cancers. Also, apart from providing an understanding of the molecular mechanisms associated with breast cancers, these cell lines have contributed significantly to areas such as drug testing. We present in this review the features of these cell lines, the studies conducted using them and the outcome of such studies. Also, the details about the culture conditions and study outcomes of the cell lines grown in 3-dimensional (3D) systems are presented.
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Affiliation(s)
- Maddaly Ravi
- Department of Human Genetics, Faculty of Biomedical Sciences, Technology and Research, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai, 600116, India.
| | - M Kaviya Sneka
- Department of Human Genetics, Faculty of Biomedical Sciences, Technology and Research, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai, 600116, India
| | - Aastha Joshipura
- Department of Human Genetics, Faculty of Biomedical Sciences, Technology and Research, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai, 600116, India
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Cabañas-García E, Areche C, Jáuregui-Rincón J, Cruz-Sosa F, Pérez-Molphe Balch E. Phytochemical Profiling of Coryphantha macromeris (Cactaceae) Growing in Greenhouse Conditions Using Ultra-High-Performance Liquid Chromatography⁻Tandem Mass Spectrometry. Molecules 2019; 24:molecules24040705. [PMID: 30781375 PMCID: PMC6412493 DOI: 10.3390/molecules24040705] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2019] [Revised: 02/11/2019] [Accepted: 02/14/2019] [Indexed: 01/08/2023] Open
Abstract
Chromatographic separation combined with mass spectrometry is a powerful tool for the characterization of plant metabolites because of its high sensitivity and selectivity. In this work, the phytochemical profile of aerial and radicular parts of Coryphantha macromeris (Engelm.) Britton & Rose growing under greenhouse conditions was qualitatively investigated for the first time by means of modern ultra-high-performance liquid chromatography⁻tandem mass spectrometry (UHPLC-PDA-HESI-Orbitrap-MS/MS). The UHPLC-PDA-HESI-Orbitrap-MS/MS analysis indicated a high complexity in phenolic metabolites. In our investigation, 69 compounds were detected and 60 of them were identified. Among detected compounds, several phenolic acids, phenolic glycosides, and organic acids were found. Within this diversity, 26 metabolites were exclusively detected in the aerial part, and 19 in the roots. Twenty-four metabolites occurred in both plant parts. According to the relative abundance of peaks in the chromatogram, ferulic and piscidic acids and their derivatives may correspond to one of the main phenolic compounds of C. macromeris. Our results contribute to the phytochemical knowledge regarding C. macromeris and its potential applications in the pharmaceutical and cosmetic industries. Besides, some metabolites and their fragmentation patterns are reported here for the first time for cacti species.
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Affiliation(s)
- Emmanuel Cabañas-García
- Centro de Ciencias Básicas, Universidad Autónoma de Aguascalientes, Av. Universidad 940, 20131 Aguascalientes, Mexico.
| | - Carlos Areche
- Departamento de Química, Facultad de Ciencias, Universidad de Chile, Casilla 653, Santiago 7800024, Chile.
| | - Juan Jáuregui-Rincón
- Centro de Ciencias Básicas, Universidad Autónoma de Aguascalientes, Av. Universidad 940, 20131 Aguascalientes, Mexico.
| | - Francisco Cruz-Sosa
- Departamento de Biotecnología, Universidad Autónoma Metropolitana-Iztapalapa. Av. San Rafael Atlixco 186, Col. Vicentina C.P., 09340 Ciudad de México, Mexico.
| | - Eugenio Pérez-Molphe Balch
- Centro de Ciencias Básicas, Universidad Autónoma de Aguascalientes, Av. Universidad 940, 20131 Aguascalientes, Mexico.
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Kim MS, Lee CW, Kim JH, Lee JC, An WG. Extract of Rhus verniciflua Stokes Induces p53-Mediated Apoptosis in MCF-7 Breast Cancer Cells. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2019; 2019:9407340. [PMID: 30881477 PMCID: PMC6383427 DOI: 10.1155/2019/9407340] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Revised: 01/04/2019] [Accepted: 01/28/2019] [Indexed: 01/05/2023]
Abstract
Rhus verniciflua Stokes has long been used as a food supplement and traditional herbal medicine for various ailments in East Asia. We evaluated the anticancer effects of Rhus verniciflua Stokes extract (RVSE) on MCF-7 cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, annexin V/7-AAD staining, and western blotting. In addition, the gallic acid content of RVSE was assayed using high-performance liquid chromatography. RVSE inhibited the growth of MCF-7 cells in a dose-dependent manner by inducing apoptosis in the sub-G1 phase. RVSE also significantly increased the number of apoptotic cells and increased the expression of p53 and p21 in a dose-dependent manner. Furthermore, RVSE treatment increased the Bax:Bcl-2 ratio and the levels of apoptosis-related factors, such as cleaved caspase-3 and -9 and PARP, in MCF-7 cells. Our findings suggest that the proapoptotic effect of RVSE on MCF-7 cells is mediated by p53, p21, and the intrinsic mitochondrial cascade. Thus, RVSE shows promise for the prevention and treatment of breast cancer.
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Affiliation(s)
- Min Sung Kim
- School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea
- Longevity life Science and Technology Institutes, Pusan National University, Busan 46241, Republic of Korea
| | - Chul Won Lee
- Research Institute for Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea
| | - Jung-Hoon Kim
- School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea
| | - Jang-Cheon Lee
- School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea
| | - Won Gun An
- School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea
- Longevity life Science and Technology Institutes, Pusan National University, Busan 46241, Republic of Korea
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Padmavathi G, Roy NK, Bordoloi D, Arfuso F, Mishra S, Sethi G, Bishayee A, Kunnumakkara AB. Butein in health and disease: A comprehensive review. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2017; 25:118-127. [PMID: 28190465 DOI: 10.1016/j.phymed.2016.12.002] [Citation(s) in RCA: 99] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/16/2016] [Revised: 12/03/2016] [Accepted: 12/11/2016] [Indexed: 06/06/2023]
Abstract
BACKGROUND The risk of suffering from many chronic diseases seems to have made no improvement despite the advancement in medications available in the modern world. Moreover, the use of synthetic chemicals as medications has proved to worsen the scenario due to the various adverse side effects associated with them. PURPOSE Extensive research on natural medicines provides ample evidence on the safety and efficacy of phytochemicals and nutraceuticals against diverse chronic ailments. Therefore, it is advisable to use natural products in the management of such diseases. This article aims to present a comprehensive and critical review of known pharmacological and biological effects of butein, an important chalcone polyphenol first isolated from Rhus verniciflua Stokes, implicated in the prevention and treatment of various chronic disease conditions. METHODS An extensive literature search was conducted using PubMed, ScienceDirect, Scopus and Web of ScienceTM core collections using key words followed by evaluation of the bibliographies of relevant articles. RESULTS Butein has been preclinically proven to be effective against several chronic diseases because it possesses a wide range of biological properties, including antioxidant, anti-inflammatory, anticancer, antidiabetic, hypotensive and neuroprotective effects. Furthermore, it has been shown to affect multiple molecular targets, including the master transcription factor nuclear factor-κB and its downstream molecules. Moreover, since it acts on multiple pathways, the chances of non-responsiveness and resistance development is reduced, supporting the use of butein as a preferred treatment option. CONCLUSION Based on numerous preclinical studies, butein shows significant therapeutic potential against various diseases. Nevertheless, well-designed clinical studies are urgently needed to validate the preclinical findings.
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Affiliation(s)
- Ganesan Padmavathi
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology, Guwahati, Assam 781 039, India
| | - Nand Kishor Roy
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology, Guwahati, Assam 781 039, India
| | - Devivasha Bordoloi
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology, Guwahati, Assam 781 039, India
| | - Frank Arfuso
- Stem Cell and Cancer Biology Laboratory, School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, West Australia 6009, Australia
| | - Srishti Mishra
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore
| | - Gautam Sethi
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore; School of Biomedical Sciences, Curtin Health Innovation Research Institute, Biosciences Research Precinct, Curtin University, Western Australia 6009, Australia.
| | - Anupam Bishayee
- Department of Pharmaceutical Sciences, College of Pharmacy, Larkin Health Sciences Institute, Miami, FL 33169, USA.
| | - Ajaikumar B Kunnumakkara
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology, Guwahati, Assam 781 039, India.
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Duan J, Guan Y, Mu F, Guo C, Zhang E, Yin Y, Wei G, Zhu Y, Cui J, Cao J, Weng Y, Wang Y, Xi M, Wen A. Protective effect of butin against ischemia/reperfusion-induced myocardial injury in diabetic mice: involvement of the AMPK/GSK-3β/Nrf2 signaling pathway. Sci Rep 2017; 7:41491. [PMID: 28128361 PMCID: PMC5269748 DOI: 10.1038/srep41491] [Citation(s) in RCA: 99] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2016] [Accepted: 12/21/2016] [Indexed: 12/30/2022] Open
Abstract
Hyperglycemia-induced reactive oxygen species (ROS) generation contributes to development of diabetic cardiomyopathy (DCM). This study was designed to determine the effect of an antioxidant butin (BUT) on ischemia/reperfusion-induced myocardial injury in diabetic mice. Myocardial ischemia/reperfusion (MI/R) was induced in C57/BL6J diabetes mice. Infarct size and cardiac function were detected. For in vitro study, H9c2 cells were used. To clarify the mechanisms, proteases inhibitors or siRNA were used. Proteins levels were investigated by Western blotting. In diabetes MI/R model, BUT significantly alleviated myocardial infarction and improved heart function, together with prevented diabetes-induced cardiac oxidative damage. The expression of Nrf2, AMPK, AKT and GSK-3β were significantly increased by BUT. Furthermore, in cultured H9c2 cardiac cells silencing Nrf2 gene with its siRNA abolished the BUT's prevention of I/R-induced myocardial injury. Inhibition of AMPK and AKT signaling by relative inhibitor or specific siRNA decreased the level of BUT-induced Nrf2 expression, and diminished the protective effects of BUT. The interplay relationship between GSK-3β and Nrf2 was also verified with relative overexpression and inhibitors. Our findings indicated that BUT protected against I/R-induced ROS-mediated apoptosis by upregulating the AMPK/Akt/GSK-3β pathway, which further activated Nrf2-regulated antioxidant enzymes in diabetic cardiomyocytes exposed to I/R.
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Affiliation(s)
- Jialin Duan
- Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, China
- College of Pharmacy, Shaanxi University of Chinese Medicine, XianYang 712083, PR China
| | - Yue Guan
- Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, China
| | - Fei Mu
- Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, China
| | - Chao Guo
- Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, China
| | - Enhu Zhang
- College of Pharmacy, Shaanxi University of Chinese Medicine, XianYang 712083, PR China
| | - Ying Yin
- Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, China
| | - Guo Wei
- Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, China
| | - Yanrong Zhu
- Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, China
| | - Jia Cui
- Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, China
| | - Jinyi Cao
- Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, China
| | - Yan Weng
- Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, China
| | - Yanhua Wang
- Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, China
| | - Miaomiao Xi
- Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, China
| | - Aidong Wen
- Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, China
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Lee EJ, Lee G, Sohn SH, Bae H. Extract of Rhus verniciflua Stokes enhances Th1 response and NK cell activity. Mol Cell Toxicol 2017. [DOI: 10.1007/s13273-016-0044-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
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Padmavathi G, Rathnakaram SR, Monisha J, Bordoloi D, Roy NK, Kunnumakkara AB. Potential of butein, a tetrahydroxychalcone to obliterate cancer. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2015; 22:1163-1171. [PMID: 26598915 DOI: 10.1016/j.phymed.2015.08.015] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/10/2015] [Revised: 08/15/2015] [Accepted: 08/23/2015] [Indexed: 06/05/2023]
Abstract
BACKGROUND Despite the major advances made in the field of cancer biology, it still remains one of the most fatal diseases in the world. It is now well established that natural products are safe and efficacious and have high potential in the prevention and treatment of different diseases including cancer. Butein is one such compound which is now found to have anti-cancer properties against various malignancies. PURPOSE To thoroughly review the literature available on the anti-cancer properties of butein against different cancers and its molecular targets. METHODS A thorough literature search has been done in PubMed for butein, its biological activities especially cancer and its molecular targets. RESULTS Our search retrieved several reports on the various biological activities of butein in which around 43 articles reported that butein shows potential anti-proliferative effect against a wide range of neoplasms and the molecular target varies with cancer types. Most often it targets NF-κB and its downstream pathways. In addition, butein induces the expression of genes which mediate the cell death and apoptosis in cancer cells. It also inhibits tumor angiogenesis, invasion and metastasis in prostate, liver and bladder cancers through the inhibition of MMPs, VEGF etc. Moreover, it inhibits the overexpression of several proteins and enzymes such as STAT3, ERK, CXCR4, COX-2, Akt, EGFR, Ras etc. involved in tumorigenesis. CONCLUSION Collectively, all these findings suggest the enormous potential and efficacy of butein as a multitargeted chemotherapeutic, chemopreventive and chemosensitizing agent against a wide range of cancers with minimal or no adverse side effects.
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Affiliation(s)
- Ganesan Padmavathi
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Assam 781039, India
| | - Sivakumar Raju Rathnakaram
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Assam 781039, India
| | - Javadi Monisha
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Assam 781039, India
| | - Devivasha Bordoloi
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Assam 781039, India
| | - Nand Kishor Roy
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Assam 781039, India
| | - Ajaikumar B Kunnumakkara
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Assam 781039, India .
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Song A, Eo W, Lee S. Comparison of selected inflammation-based prognostic markers in relapsed or refractory metastatic colorectal cancer patients. World J Gastroenterol 2015; 21:12410-12420. [PMID: 26604648 PMCID: PMC4649124 DOI: 10.3748/wjg.v21.i43.12410] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2015] [Revised: 06/30/2015] [Accepted: 09/02/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the impact of systemic inflammation-based prognostic markers on overall survival in relapsed/refractory metastatic colorectal cancer (mCRC) patients.
METHODS: To investigate prognostic markers in mCRC patients, this study was performed with patients who have experienced relapsed/refractory mCRC with standard chemotherapy or were inapplicable to conventional treatment modality because of poor performance status, age, or comorbidity. We reviewed the medical records of 177 mCRC patients managed with Korean Medicine (KM) treatment modality using an anticancer agent of Rhus verniciflua Stokes extract from June 2006 to April 2013. The clinicopathologic characteristics, laboratory test, the systemic inflammation markers including the modified Glasgow prognostic score (mGPS), neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), lymphocyte monocyte ratio (LMR), and prognostic nutritional index (PNI) were analyzed. The overall survival of patients was calculated with the Kaplan-Meier method and the statistical significance was compared using with the log-rank test. To compare the impact of systemic inflammation based markers, the hazard ratio (HR) of mGPS, NLR, PLR, LMR, and PNI for overall survival were evaluated with the Cox proportional hazards regression.
RESULTS: The majority of mCRC patients had relapsed/refractory to standard chemotherapy; 128 patients (72.3%) had undergone more than second line chemotherapy, and the median time from diagnosis of mCRC to initiation of KM was 9.4 mo. The median overall survival of enrolled patients was 8.3 mo. On univariate analyses, the inflammation markers of higher mGPS (P < 0.001), NLR ≥ 5 (P < 0.001), PLR > 300 (P = 0.004), LMR ≤ 3.4 (P < 0.001), and PNI ≤ 45.3 (P = 0.001) were significantly associated with decreased survival time. On stepwise multivariate proportional hazards model, mGPS at 2 vs 0 (HR = 3.212, 95%CI: 1.437-7.716, P = 0.004), and LMR ≤ 3.4 (HR = 1.658, 95%CI: 1.092-2.518, P = 0.018) as independent predictors associated with poor overall survival along with carbohydrate antigen 19-9 (HR = 1.482, 95%CI: 1.007-2.182, P = 0.046), AST ≥ 40 (HR = 2.377, 95%CI: 1.359-4.155, P = 0.002), and the treatment duration for KM less than 2.9 mo (HR = 1.718, 95%CI: 1.160-2.543, P = 0.007).
CONCLUSION: These results indicate that the inflammatory markers, mGPS and LMR are independent prognostic factors for predicting overall survival in relapsed/refractory mCRC patients.
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Lee WJ, Kang JE, Choi JH, Jeong ST, Kim MK, Choi HS. Comparison of the Flavonoid and Urushiol Content in Different Parts of Rhus verniciflua Stokes Grown in Wonju and Okcheon. ACTA ACUST UNITED AC 2015. [DOI: 10.9721/kjfst.2015.47.2.158] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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Kim KH, Moon E, Choi SU, Pang C, Kim SY, Lee KR. Identification of cytotoxic and anti-inflammatory constituents from the bark of Toxicodendron vernicifluum (Stokes) F.A. Barkley. JOURNAL OF ETHNOPHARMACOLOGY 2015; 162:231-237. [PMID: 25582488 DOI: 10.1016/j.jep.2014.12.071] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/16/2014] [Revised: 12/26/2014] [Accepted: 12/30/2014] [Indexed: 06/04/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Toxicodendron vernicifluum (Stokes) F.A. Barkley (Anacardiaceae) has traditionally been used as a food supplement and in traditional herbal medicine to treat inflammatory diseases and cancers for centuries in Korea. This study was designed to isolate the bioactive constituents from the ethanol extract of Toxicodendron vernicifluum bark and evaluate their cytotoxic and anti-inflammatory activities. MATERIAL AND METHODS Bioassay-guided fractionation and chemical investigation of the ethanol extract of Toxicodendron vernicifluum bark resulted in the isolation and identification of three new polyphenols (1-3) and six flavonoids (4-9). The structures of the isolated compounds were elucidated by spectroscopic analysis, including 1D and 2D nuclear magnetic resonance (NMR) ((1)H, (13)C, COSY, HMQC and HMBC experiments), and high resolution (HR)-mass spectrometry, and their absolute configurations were further confirmed by chemical methods and circular dichroism (CD) data analysis. Compounds 1-9 were evaluated for their antiproliferative activities against four human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and HCT-15), and anti-inflammatory activities by measuring nitric oxide (NO) levels in the medium of murine microglia BV-2 cells. RESULTS The isolated compounds were characterized as in the following: three new polyphenols, rhusopolyphenols G-I (1-3) and six flavonoids including two aurones, 2-benzyl-2,3',4',6-tetrahydroxybenzo[b]furan-3(2H)-one (4), sulfuretin (5), two dihydroflavonols, (+)-(2S,3R)-fustin (6), (+)-epitaxifolin (7), one chalcone, butein (8), and one flavonol, fisetin (9). The published NMR assignments of 4 were corrected by the detailed analysis of spectroscopic data in this study. Among the tested compounds, compounds 4-9 showed antiproliferative activity against the tested cells, with IC50 values of 4.78-28.89 μM. Compounds 5 and 8 significantly inhibited NO production in lipopolysaccharide (LPS)-stimulated BV-2 cells with IC50 values of 23.37 and 11.68 μM, respectively. CONCLUSIONS Polyphenols including flavonoids were one of the main constituents of Toxicodendron vernicifluum bark, and activities demonstrated by the isolated compounds support the ethnopharmacological use of Toxicodendron vernicifluum as anti-cancer and/or anti-inflammatory agents.
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Affiliation(s)
- Ki Hyun Kim
- Natural Products Laboratory, School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea
| | - Eunjung Moon
- College of Pharmacy, Gachon University, #191 Hambakmoero, Yeonsu-gu, Incheon 406-799, Republic of Korea
| | - Sang Un Choi
- Korea Research Institute of Chemical Technology, Deajeon 305-600, Republic of Korea
| | - Changhyun Pang
- School of Chemical Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea
| | - Sun Yeou Kim
- College of Pharmacy, Gachon University, #191 Hambakmoero, Yeonsu-gu, Incheon 406-799, Republic of Korea
| | - Kang Ro Lee
- Natural Products Laboratory, School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
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Hosseini A, Ghorbani A. Cancer therapy with phytochemicals: evidence from clinical studies. AVICENNA JOURNAL OF PHYTOMEDICINE 2015; 5:84-97. [PMID: 25949949 PMCID: PMC4418057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Received: 08/05/2014] [Revised: 01/08/2015] [Accepted: 01/18/2015] [Indexed: 11/28/2022]
Abstract
Cancer is still one of the major causes of mortality in both developing and developed countries. At present, in spite of intensive interventions, a large number of patients suffer from poor prognosis. Therefore, the effort for finding new anticancer agents with better efficacy and lesser side effects has been continued. According to the traditional recommendations and experimental studies, numerous medicinal plants have been reported to have anticancer effect. Also antiproliferative, pro-apoptotic, anti-metastatic and anti-angiogenic effects of several phytochemicals have been shown in in vitro experiments or animal studies. However, only a small number have been tested in cancerous patients and limited evidence exists for their clinical effectiveness. Also, regarding some phytochemicals, only beneficial effects on cancer-related symptoms or on quality of life have been reported and no positive results exist for their antitumor actions. This review was focused on the phytochemicals whole beneficial effects on various types of cancer have been supported by clinical trials. Based on the literature review, curcumin, green tea, resveratrol and Viscum album were the satisfactory instances of clinical evidence for supporting their anticancer effects. The main findings of these phytochemicals were also summarized and discussed.
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Affiliation(s)
- Azar Hosseini
- Pharmacological Research Center of Medicinal Plants, School of Medicine, Mashhad University of Medical Sciences, Iran
| | - Ahmad Ghorbani
- Pharmacological Research Center of Medicinal Plants, School of Medicine, Mashhad University of Medical Sciences, Iran,Neurogenic Inflammation Research Centre, Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran,Corresponding Author: Tel: 05138002283, Fax: 05138828567, ghorbania @mums.ac.ir
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Kim JH, Shin YC, Ko SG. Integrating traditional medicine into modern inflammatory diseases care: multitargeting by Rhus verniciflua Stokes. Mediators Inflamm 2014; 2014:154561. [PMID: 25024508 PMCID: PMC4082934 DOI: 10.1155/2014/154561] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2014] [Revised: 04/03/2014] [Accepted: 04/03/2014] [Indexed: 01/05/2023] Open
Abstract
Despite the fact that numerous researches were performed on prevention and treatment of inflammation related diseases, the overall incidence has not changed remarkably. This requires new approaches to overcome inflammation mediated diseases, and thus traditional medicine could be an efficacious source for prevention and treatment of these diseases. In this review, we discuss the contribution of traditional medicine, especially Rhus verniciflua Stokes, to modern medicine against diverse inflammation mediated diseases. Traditionally, this remedy has been used in Eastern Asia for the treatment of gastric problems, hepatic disorders, infectious diseases, and blood disorders. Modern science has provided the scientific basis for the use of Rhus verniciflua Stokes against such disorders and diseases. Various chemical constituents have been identified from this plant, including phenolic acid, and flavonoids. Cell-based studies have exhibited the potential of this as antibacterial, antioxidant, neuroprotective, anti-inflammatory, growth inhibitory, and anticancer activities. Enormous animal studies have shown the potential of this against proinflammatory diseases, neurodegenerative diseases, diabetes, liver diseases, and chemical insults. At the molecular level, this medicinal plant has been shown to modulate diverse cell-signaling pathways. In clinical studies, Rhus verniciflua Stokes has shown efficacy against various cancer patients such as colorectal, gastric, hepatic, renal, pancreatic, and pulmonary cancers. Thus, this remedy is now exhibiting activities in the clinic.
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Affiliation(s)
- Ji Hye Kim
- Laboratory of Clinical Biology and Pharmacogenomics, Department of Preventive Medicine, College of Oriental Medicine, Kyunghee University, 1 Hoegi-dong, Seoul 130-701, Republic of Korea
| | - Yong Cheol Shin
- Laboratory of Clinical Biology and Pharmacogenomics, Department of Preventive Medicine, College of Oriental Medicine, Kyunghee University, 1 Hoegi-dong, Seoul 130-701, Republic of Korea
| | - Seong-Gyu Ko
- Laboratory of Clinical Biology and Pharmacogenomics, Department of Preventive Medicine, College of Oriental Medicine, Kyunghee University, 1 Hoegi-dong, Seoul 130-701, Republic of Korea
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LI YANG, MA CHENGYUAN, QIAN MING, WEN ZHONGMEI, JING HONGYU, QIAN DONGHUA. Butein induces cell apoptosis and inhibition of cyclooxygenase-2 expression in A549 lung cancer cells. Mol Med Rep 2013; 9:763-7. [DOI: 10.3892/mmr.2013.1850] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2013] [Accepted: 11/29/2013] [Indexed: 11/05/2022] Open
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Kim KH, Moon E, Choi SU, Kim SY, Lee KR. Polyphenols from the bark of Rhus verniciflua and their biological evaluation on antitumor and anti-inflammatory activities. PHYTOCHEMISTRY 2013; 92:113-121. [PMID: 23752101 DOI: 10.1016/j.phytochem.2013.05.005] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/13/2012] [Revised: 02/27/2013] [Accepted: 05/08/2013] [Indexed: 06/02/2023]
Abstract
Bioassay-guided fractionation and chemical investigation of the extract of Rhus verniciflua bark resulted in the identification of six polyphenols, rhusopolyphenols A-F (1-6), together with four known compounds including (2R,3S,10S)-7,8,9,13-tetrahydroxy-2-(3,4-dihydroxyphenyl)-2,3-trans-3,4-cis-2,3,10-trihydrobenzopyrano[3,4-c]-2-benzopyran-1-one (7), peapolyphenol C (8), cilicione-b (9) and (αR)-α,3,4,2',4'-pentahydroxydihydrochalcone (10). The structures of these polyphenols were elucidated by spectroscopic analysis, including 1D and 2D NMR, and HR-ESIMS, and their absolute configurations were further confirmed by a combination of chemical methods and CD data analysis. All isolates were evaluated for their antiproliferative activities against four human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and HCT-15), and compounds 4-6, 9 and 10 showed antiproliferative activity against the tested cells, with IC50 values of 3.31-18.51 μM. On the basis of the expanded understanding that inflammation is a crucial cause of tumor progression, the anti-inflammatory activities of these compounds were determined by measuring nitric oxide (NO) levels in the medium of murine microglia BV-2 cells. Compounds 5 and 10 significantly inhibited NO production in lipopolysaccharide (LPS)-stimulated murine microglia BV-2 cells with IC50 values of 28.90 and 12.70 μM, respectively.
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Affiliation(s)
- Ki Hyun Kim
- Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA
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In vitro and in vivo antidermatophytic activity of the dichloromethane-methanol (1:1 v/v) extract from the stem bark of Polyscias fulva Hiern (Araliaceae). Altern Ther Health Med 2013; 13:95. [PMID: 23641972 PMCID: PMC3658906 DOI: 10.1186/1472-6882-13-95] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2012] [Accepted: 04/29/2013] [Indexed: 11/23/2022]
Abstract
Background During the last decades, the number of people suffering from dermatophytoses has seriously increased, mainly due to the development of resistant strains of microorganisms to a range of formally efficient antibiotics. Polyscias fulva, a medium size tree which grows in the West Region of Cameroon is traditionally used for local application against dermatoses and orally against venereal infections. The dichloromethane-methanol (1:1 v/v) extract from the stem bark of Polyscias fulva was evaluated for its in vitro and in vivo antifungal activities. Methods The plant extract was prepared by maceration of its stem bark powder in CH2Cl2-MeOH (1:1 v/v). The extract obtained was successively partitioned in hexane, ethyl acetate and n-butanol. Phytochemical screening was performed using standard methods. In vitro antidermatophytic activity was assayed by the well diffusion and broth microdilution methods. The degree of dermal irritation of the crude extract was determined in guinea pigs using the occluded dermal irritation test method. The in vivo antidermatophytic activity of the extract-oil formulation (1.25, 2.5 and 5% w/w concentrations) was evaluated using Trichophyton mentagrophytes-induced dermatophytosis in a guinea pigs model. Results Phytochemical screening indicated that, the crude extract, ethyl acetate, n-butanol and residue fractions contain in general saponins, tannins, alkaloids, anthraquinones and phenols while the hexane fraction contains only alkaloids. The ethyl-acetate, n-butanol and residue fractions displayed higher antifungal activities (MIC = 0.125-0.5 mg.mL-1) against eight dermatophytes as compared to the crude extract (MIC = 0.5-1 mg.mL-1). This latter appeared to have slight perceptible erythema effects on guinea pigs as the primary irritation index (PII) was calculated to be 0.54. In vivo, the antidermatophytic activities of the extract-oil formulations were dose-dependent. Griseofulvin-oil 5% at 0.01 g/kg and formulated extract-oil (5%) at 0.1 g/kg eradicated the microbial infection after thirteen and fourteen days of daily treatment respectively. Conclusions The results of preclinical in vitro and in vivo evaluations indicate that the extract-oil formulation at 5% may constitute an alternative means to alleviate fungal infections caused by dermatophytes.
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Kapoor S. Butein and its emerging anti-proliferative and pro-apoptotic effects in systemic malignancies. Curr Eye Res 2013; 38:810. [PMID: 23621171 DOI: 10.3109/02713683.2013.785571] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Impact of Standardized Allergen-Removed Rhus verniciflua Stokes Extract on Advanced Adenocarcinoma of the Ampulla of Vater: A Case Series. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2013; 2013:203168. [PMID: 23710214 PMCID: PMC3654714 DOI: 10.1155/2013/203168] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/02/2013] [Accepted: 04/03/2013] [Indexed: 12/29/2022]
Abstract
Background. Adenocarcinoma of the ampulla of Vater (AAV) is a rare malignancy that has a better prognosis than other periampullary cancers. However, the standard treatment for patients with relapsed or metastatic AAV has not been established. We investigated the clinical feasibility of standardized allergen-removed Rhus verniciflua stokes (aRVS) extract for advanced or metastatic AAV. Patients and Methods. From July 2006 to April 2011, we retrospectively reviewed all patients with advanced AAV treated with aRVS extract alone. After applying inclusion/exclusion criteria, 12 patients were eligible for the final analysis. We assessed the progression-free survival (PFS) and overall survival (OS) of these patients during the follow-up period. Results. The median aRVS administration period was 147.0 days (range: 72–601 days). The best tumor responses according to Response Evaluation Criteria in Solid Tumors were as follows: two with complete response, two with stable disease, and eight with progressive disease. The median OS was 15.1 months (range: 4.9–25.1 months), and the median PFS was 3.0 months (range: 1.6–11.4 months). Adverse reactions to the aRVS treatment were mostly mild and self-limiting. Conclusions. Prolonged survival was observed in patients with advanced AAV under the treatment of standardized aRVS extract without significant adverse effects.
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An update on antitumor activity of naturally occurring chalcones. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2013; 2013:815621. [PMID: 23690855 PMCID: PMC3652162 DOI: 10.1155/2013/815621] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/15/2013] [Accepted: 03/19/2013] [Indexed: 12/20/2022]
Abstract
Chalcones, which have characteristic 1,3-diaryl-2-propen-1-one skeleton, are mainly produced in roots, rhizomes, heartwood, leaves, and seeds of genera Angelica, Sophora, Glycyrrhiza, Humulus, Scutellaria, Parartocarpus, Ficus, Dorstenia, Morus, Artocarpus, and so forth. They have become of interest in the research and development of natural antitumor agents over the past decades due to their broad range of mechanisms including anti-initiation, induction of apoptosis, antiproliferation, antimetastasis, antiangiogenesis, and so forth. This review summarizes the studies on the antitumor activity of naturally occurring chalcones and their underlying mechanisms in detail during the past decades.
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Butein protects human dental pulp cells from hydrogen peroxide-induced oxidative toxicity via Nrf2 pathway-dependent heme oxygenase-1 expressions. Toxicol In Vitro 2013; 27:874-81. [PMID: 23318726 DOI: 10.1016/j.tiv.2013.01.003] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2012] [Revised: 12/10/2012] [Accepted: 01/03/2013] [Indexed: 01/03/2023]
Abstract
Rhus verniciflua Stokes is a plant that is native to East Asian countries, such as Korea, China, and Japan. Butein, a plant polyphenol, is one of the major active components of R. verniciflua. Reactive oxygen species (ROS), produced via dental adhesive bleaching agents and pulpal disease, can cause oxidative stress. Here, we found that butein possesses cytoprotective effects on hydrogen peroxide (H2O2)-induced dental cell death. H2O2 is a representative ROS and causes cell death through necrosis in human dental pulp (HDP) cells. H2O2-induced cytotoxicity and production of ROS were blocked in the presence of butein, and these effects were dose dependent. Butein also increased heme oxygenase-1 (HO-1) protein expression and HO activity. In addition, butein-dependent HO-1 expression was required for the inhibition of H2O2-induced cell death and ROS generation. Furthermore, butein treatment caused nuclear accumulation of nuclear factor-E2-related factor 2 (Nrf2) and increased the promoter activity of antioxidant response elements (AREs). Treatment of HDP cells with a c-Jun NH2-terminal kinase (JNK) inhibitor also reduced butein-induced HO-1 expression, and butein treatment led to increased JNK phosphorylation. These results indicate that butein may be used to prevent functional dental cell death and thus may be useful as a pulpal disease agent.
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Lee KW, Chung KS, Seo JH, Yim SV, Park HJ, Choi JH, Lee KT. Sulfuretin from heartwood of Rhus verniciflua triggers apoptosis through activation of Fas, Caspase-8, and the mitochondrial death pathway in HL-60 human leukemia cells. J Cell Biochem 2012; 113:2835-44. [PMID: 22492309 DOI: 10.1002/jcb.24158] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Sulfuretin, a flavonoid isolated from heartwood of Rhus verniciflua, has been reported to have anti-cancer activities but the underlying molecular mechanism was not clear. In this study, sulfuretin induced apoptosis by activating caspases-8, -9, and -3 as well as cleavage of poly(ADP-ribose) polymerase. Furthermore, treatment with sulfuretin caused mitochondrial dysfunctions, including the loss of mitochondrial membrane potential (ΔΨ(m)), the release of cytochrome c to the cytosol, and the translocations of Bax and tBid. Sulfuretin also activated the extrinsic apoptosis pathway, that is, it increased the expressions of Fas and FasL, the activation of caspase-8, and the cleavage of Bid. Furthermore, blocking the FasL-Fas interaction with NOK-1 monoclonal antibody prevented the sulfuretin-induced apoptosis. The therapeutical effect of sulfuretin in leukemia is due to its potent apoptotic activity through the extrinsic pathway driven by a Fas-mediated caspase-8-dependent pathway.
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Affiliation(s)
- Kyung-Won Lee
- Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea
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Choi SJ, Lee MY, Jo H, Lim SS, Jung SH. Preparative isolation and purification of neuroprotective compounds from Rhus verniciflua by high speed counter-current chromatography. Biol Pharm Bull 2012; 35:559-67. [PMID: 22466561 DOI: 10.1248/bpb.35.559] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
In the present study, extracts from Rhus verniciflua were demonstrated to significantly attenuate the negative effects of hydrogen peroxide (H(2)O(2)) on transformed retinal ganglion cell line (RGC-5 cells), indicating that they may be protective against oxidative stress-induced retinal degeneration. The inclusion of R. verniciflua in the culture was found to both reduce the levels of reactive oxygen species (ROS) present and lessen the up-regulation of apoptotic proteins such as cleaved poly(ADP-ribose) polymerase, cleaved caspase-3, and cleaved caspase-9. Active compounds were also successfully isolated from R. verniciflua using high-speed counter-current chromatography (HSCCC) with a two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water (3.5:5:3.5:5, v/v). Using this method, we successfully separated 252.1 mg of fustin at a purity of over 93.09%, 51.2 mg of fisetin at a purity of over 95.45%, 39.7 mg of sulfuretin at a purity of over 95.17%, and 10.7 mg of butein at a purity of over 95.01% from 1.5 g of R. verniciflua extract. The chemical structures of these compounds were elucidated by chemical and spectral analyses. There isolated compounds also significantly attenuated the negative effects of H(2)O(2) on RGC-5 cells. Results therefore suggest that, due to its anti-oxidative and anti-apoptotic effects, R. verniciflua could be used as a lead substance for the treatment of retinal diseases such as glaucoma.
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Affiliation(s)
- Soon Jung Choi
- Functional Food Center, Korea Institute of Science and Technology, Gangneung Institute, Republic of Korea
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Khan N, Adhami VM, Afaq F, Mukhtar H. Butein induces apoptosis and inhibits prostate tumor growth in vitro and in vivo. Antioxid Redox Signal 2012; 16:1195-204. [PMID: 22114764 PMCID: PMC3324811 DOI: 10.1089/ars.2011.4162] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
AIM Prostate cancer (PCa) is one of the most common cancers in men in the United States with similar trends worldwide. For several reasons, it is an ideal candidate disease for intervention with dietary botanical antioxidants. Indeed, many botanical antioxidants are showing promise for chemoprevention of PCa. Here, we determined the effect of an antioxidant butein (3,4,2',4'-tetrahydroxychalone) on cell growth, apoptosis, and signaling pathways in human PCa cells in-vitro and on tumor growth in athymic nude mice. RESULTS Treatment with butein (10-30 μM; 48 h) caused a decrease in viability of PCa cells but had only a minimal effect on normal prostate epithelial cells. In butein-treated cells, there was a marked decrease in the protein expression of cyclins D1, D2, and E and cdks 2, 4, and 6 with concomitant induction of WAF1/p21 and KIP1/p27. Treatment of cells with butein caused inhibition of (i) phosphatidylinositol 3-kinase (p85 and p110), (ii) phosphorylation of Akt at both Ser(473) and Thr(308), (iii) nuclear factor-kappa B (NF-κB) and IκB kinaseα, (iv) degradation and phosphorylation of IκBα, (v) NF-κB DNA-binding activity, (vi) induction of apoptosis, and (vii) Poly (ADP-ribose) polymerase cleavage with activation of caspases-3, -8, and -9. Pretreatment of cells with caspase inhibitor (Z-VAD-FMK) blocked butein-induced activation of caspases. In athymic nude mice implanted with human PCa cells, butein caused a significant inhibition of tumor growth with a decrease in the serum prostate-specific antigen levels. INNOVATION For the first time, we have shown that butein caused inhibition of prostate tumor growth in-vivo. CONCLUSION We suggest that butein could be developed as an agent against PCa. Antioxid. Redox Signal. 16, 1195-1204.
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Affiliation(s)
- Naghma Khan
- Department of Dermatology, University of Wisconsin, Madison, WI 53706, USA
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Cui Z, Song E, Hu DN, Chen M, Rosen R, McCormick SA. Butein induces apoptosis in human uveal melanoma cells through mitochondrial apoptosis pathway. Curr Eye Res 2012; 37:730-9. [PMID: 22578288 DOI: 10.3109/02713683.2012.671436] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
PURPOSE To study the cytotoxic effects and related signaling pathways of butein on human uveal melanoma cells in vitro. MATERIALS AND METHODS Three human uveal melanoma cell lines (M17, SP6.5, and C918), retinal pigment epithelial (RPE) cells and scleral fibroblasts were treated with butein at different dosages. The effects of butein on cell viability were assessed by using the MTT assay. Cell apoptosis was determined using annexin V-FITC/ethidium homodimer III flow cytometry. Mitochondrial transmembrane potential changes were assessed by using the JC-1 fluorescent reader, cytosol cytochrome c levels, and the activities of caspase-3, -8, and -9 were measured by using an enzyme-linked immunosorbent assay or colorimetric assay. RESULTS Butein reduced the cell viability of cultured human uveal melanoma cells in a dose-dependent manner (10, 30, and 100 μM), with IC50 at 13.3 μM and 15.8 μM in SP6.5 and M17 cell lines, respectively. Similar effects were also found in a highly aggressive and metastatic C918 cell line (IC50 16.7 μM). Butein at lower concentrations (10-30 μM) selectively reduced the cell viability of uveal melanoma cells, without affecting cell viability of RPE cells and fibroblasts. Butein-induced apoptosis of melanoma cells, increased mitochondrial permeability and the level of cytosol cytochrome c, caspase-9 and -3 activities (but not caspase-8) in a dose-dependent manner. CONCLUSIONS Butein has selectively potent pro-apoptotic effects on cultured human uveal melanoma cells via the intrinsic mitochondrial pathway.
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Affiliation(s)
- Zhihua Cui
- Department of Ophthalmology, The First Hospital, Jilin University, Changchun, China
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Lee S, Kim K, Jung H, Lee S, Cheon S, Kim S, Eo W, Choi W. Efficacy and safety of standardized allergen-removed Rhus verniciflua Stokes extract in patients with advanced or metastatic pancreatic cancer: a Korean single-center experience. Oncology 2011; 81:312-8. [PMID: 22179506 DOI: 10.1159/000334695] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2011] [Accepted: 10/22/2011] [Indexed: 01/05/2023]
Abstract
BACKGROUND Pancreatic cancer has the worst prognosis because of poor response to conventional therapy. We investigated the clinical feasibility of the standardized allergen-removed Rhus verniciflua Stokes (aRVS) extract as a potential therapeutic agent for advanced or metastatic pancreatic cancer. PATIENTS AND METHODS From July 2006 to June 2010, patients with advanced or metastatic pancreatic adenocarcinoma were checked in our institution. After applying inclusion/exclusion criteria, 42 patients were eligible for the final analysis. Overall survival, clinical benefit and adverse events of these patients treated with aRVS in the aftercare period were determined. RESULTS In May 2011, 39 patients had died and the remaining 3 patients were alive with evidence of disease. The mean RVS administration period was 3.86 months (95% confidence interval 2.52-5.20). The median overall survival for the entire population was 7.87 months (95% confidence interval 5.14-10.59), and the 1-year survival rate was 26.2%, which is compatible with external controls. Using univariate and multivariate analyses, aRVS treatment including performance status and prognostic index significantly affected overall survival. A clinical benefit response was also shown by aRVS treatment which was not dependent on concurrent chemotherapy. Adverse reactions to aRVS treatment were mostly mild and self-limiting. CONCLUSIONS The standardized aRVS extract might be beneficial for patients with advanced or metastatic pancreatic cancer since it positively affected overall survival and clinical symptoms without significant adverse effects.
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Affiliation(s)
- Sanghun Lee
- Department of Clinical Oncology, Integrative Cancer Center, Kyunghee University Hospital at Gangdong, Seoul, Republic of Korea
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Rhus verniciflua stokes against advanced cancer: a perspective from the Korean Integrative Cancer Center. J Biomed Biotechnol 2011; 2012:874276. [PMID: 22174564 PMCID: PMC3228301 DOI: 10.1155/2012/874276] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2011] [Revised: 09/08/2011] [Accepted: 09/08/2011] [Indexed: 01/05/2023] Open
Abstract
Active anticancer molecules have been searched from natural products; many drugs were developed from either natural products or their derivatives following the conventional pharmaceutical paradigm of drug discovery. However, the advances in the knowledge of cancer biology have led to personalized medicine using molecular-targeted agents which create new paradigm. Clinical benefit is dependent on individual biomarker and overall survival is prolonged through cytostatic rather than cytotoxic effects to cancer cell. Therefore, a different approach is needed from the single lead compound screening model based on cytotoxicity. In our experience, the Rhus verniciflua stoke (RVS) extract traditionally used for cancer treatment is beneficial to some advanced cancer patients though it is herbal extract not single compound, and low cytotoxic in vitro. The standardized RVS extract's action mechanisms as well as clinical outcomes are reviewed here. We hope that these preliminary results would stimulate different investigation in natural products from conventional chemicals.
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Ma CY, Ji WT, Chueh FS, Yang JS, Chen PY, Yu CC, Chung JG. Butein inhibits the migration and invasion of SK-HEP-1 human hepatocarcinoma cells through suppressing the ERK, JNK, p38, and uPA signaling multiple pathways. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2011; 59:9032-9038. [PMID: 21770460 DOI: 10.1021/jf202027n] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/31/2023]
Abstract
Liver cancer is one of the most commonly diagnosed cancers and the leading cause of death in human populations. Butein, a tetrahydroxychalcone, has been shown to induce apoptosis in many human cancer cells, but the effects of butein on the migration and invasion of human liver cancer cells are not reported. Herein, we found that butein is effective in the suppression of migration and invasion in SK-HEP-1 human hepatocarcinoma cells by using the Matrigel cell migration assay and invasion system. The gelatin zymography assay indicated that butein inhibited the activity of matrix metalloproteinases 2 (MMP-2) and MMP-9. Western blotting analysis indicated that butein decreased the levels of MMP-2, -7, and -9, uPA, Ras, Rho A, ROCK1, ERK1/2, JNK1/2, p-p38, and p-c-Jun in SK-HEP-1 cells. Furthermore, butein inhibited the NF-κB binding activity in SK-HEP-1 cells by electrophoretic mobility shift assay. We also found that butein decreased the ERK, JNK, and p38 in SK-HEP-1 cells by in vitro kinase assay. In conclusion, this is the first study to demonstrate that butein might be a novel anticancer agent for the treatment of hepatocarcinoma through inhibiting migration and invasion.
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Affiliation(s)
- Chia-Yu Ma
- Department of Food and Beverage Management, Technology and Science Institute of Northern Taiwan, Taipei, Taiwan
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Jeong GS, Lee DS, Song MY, Park BH, Kang DG, Lee HS, Kwon KB, Kim YC. Butein from Rhus verniciflua protects pancreatic β cells against cytokine-induced toxicity mediated by inhibition of nitric oxide formation. Biol Pharm Bull 2011; 34:97-102. [PMID: 21212525 DOI: 10.1248/bpb.34.97] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Butein (3,4,2',4'-tetrahydroxychalcone), a plant polyphenol, is a major component in isolate of Rhus verniciflua STOKES (Anacardiaceae). It is shown to exert various potent effects such as antioxidant, antiinflammatory induction of apoptosis among many properties. In this study, we investigated the effect of butein on cytokine-induced β-cell damage. Pre-treatment with butein is shown to increase the viability of cytokine-treated INS-1 cells at concentrations of 15-30 µM. Butein prevented cytokine-mediated cell death, as well as nitric oxide (NO) production, and these effects correlated well with reduced levels of protein expression of the inducible nitric oxide synthase (iNOS). Furthermore, the molecular mechanisms by which butein inhibits iNOS gene expression appeared to be through the inhibition of nuclear factor-κB (NF-κB) translocation. In a second set of experiments, rat islets were used to demonstrate the protective effects of butein and the results were essentially the same as those observed in Beutin pretreated INS-1 cells. Butein prevented cytokine-induced NO production, iNOS expression, and NF-κB translocation and inhibition of glucose-stimulated insulin secretion (GSIS). In conclusion, these results suggest that butein can be used for the prevention of functional β-cell damage and preventing the progression of Type 1 diabetes mellitus (T1DM).
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Affiliation(s)
- Gil-Saeng Jeong
- Zoonosis Research Center, Wonkwang University, Iksan, Jeonbuk 570–749, Republic of Korea
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Orlikova B, Tasdemir D, Golais F, Dicato M, Diederich M. Dietary chalcones with chemopreventive and chemotherapeutic potential. GENES AND NUTRITION 2011; 6:125-47. [PMID: 21484163 DOI: 10.1007/s12263-011-0210-5] [Citation(s) in RCA: 159] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/23/2010] [Accepted: 01/06/2011] [Indexed: 02/07/2023]
Abstract
Chalcones are absorbed in the daily diet and appear to be promising cancer chemopreventive agents. Chalcones represent an important group of the polyphenolic family, which includes a large number of naturally occurring molecules. This family possesses an interesting spectrum of biological activities, including antioxidative, antibacterial, anti-inflammatory, anticancer, cytotoxic, and immunosuppressive potential. Compounds of this family have been shown to interfere with each step of carcinogenesis, including initiation, promotion and progression. Moreover, numerous compounds from the family of dietary chalcones appear to show activity against cancer cells, suggesting that these molecules or their derivatives may be considered as potential anticancer drugs. This review will focus primarily on prominent members of the chalcone family with an 1,3-diphenyl-2-propenon core structure. Specifically, the inhibitory effects of these compounds on the different steps of carcinogenesis that reveal interesting chemopreventive and chemotherapeutic potential will be discussed.
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Affiliation(s)
- Barbora Orlikova
- Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Fondation de Recherche Cancer et Sang, Hôpital Kirchberg, 9 Rue Edward Steichen, 2540, Luxembourg, Luxembourg
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Rajendran P, Ong TH, Chen L, Li F, Shanmugam MK, Vali S, Abbasi T, Kapoor S, Sharma A, Kumar AP, Hui KM, Sethi G. Suppression of signal transducer and activator of transcription 3 activation by butein inhibits growth of human hepatocellular carcinoma in vivo. Clin Cancer Res 2010; 17:1425-39. [PMID: 21131551 DOI: 10.1158/1078-0432.ccr-10-1123] [Citation(s) in RCA: 117] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
PURPOSE Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and the third cause of global cancer mortality. Increasing evidence suggest that STAT3 is a critical mediator of oncogenic signaling in HCC and controls the expression of several genes involved in proliferation, survival, metastasis, and angiogenesis. Thus, the novel agents that can suppress STAT3 activation have potential for both prevention and treatment of HCC. EXPERIMENTAL DESIGN The effect of butein on STAT3 activation, associated protein kinases, STAT3-regulated gene products, cellular proliferation, and apoptosis was investigated. The in vivo effect of butein on the growth of human HCC xenograft tumors in male athymic nu/nu mice was also examined. RESULTS We tested an agent, butein, for its ability to suppress STAT3 activation in HCC cells and nude mice model along with prospectively testing the hypothesis of STAT3 inhibition in a virtual predictive functional proteomics tumor pathway technology platform. We found that butein inhibited both constitutive and inducible STAT3 activation in HCC cells. The suppression was mediated through the inhibition of activation of upstream kinases c-Src and Janus-activated kinase 2. Butein inhibited proliferation and significantly potentiated the apoptotic effects of paclitaxel and doxorubicin in HCC cells. When administered intraperitoneally, butein inhibited the growth of human HCC xenograft tumors in male athymic nu/nu mice. CONCLUSIONS Overall, cumulative results from experimental and predictive studies suggest that butein exerts its antiproliferative and proapoptotic effects through suppression of STAT3 signaling in HCC both in vitro and in vivo.
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Affiliation(s)
- Peramaiyan Rajendran
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
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Moon DO, Choi YH, Moon SK, Kim WJ, Kim GY. Butein suppresses the expression of nuclear factor-kappa B-mediated matrix metalloproteinase-9 and vascular endothelial growth factor in prostate cancer cells. Toxicol In Vitro 2010; 24:1927-34. [DOI: 10.1016/j.tiv.2010.08.002] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2010] [Revised: 08/02/2010] [Accepted: 08/03/2010] [Indexed: 10/19/2022]
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Butein downregulates phorbol 12-myristate 13-acetate-induced COX-2 transcriptional activity in cancerous and non-cancerous breast cells. Eur J Pharmacol 2010; 648:24-30. [PMID: 20826149 DOI: 10.1016/j.ejphar.2010.08.015] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2010] [Revised: 07/20/2010] [Accepted: 08/21/2010] [Indexed: 02/08/2023]
Abstract
Butein is a flavonoid isolated from the bark of Rhus verniciflua Stokes and the flowers of Butea monosperma, and is known to be a potential therapeutic drug for treating inflammation and cancer. Cyclooxygenase (COX) converts arachidonic acid to prostanoids, and increased expression of its isoform COX-2 has been observed in breast cancer tissues. It has been suggested that COX inhibitors can be used as chemopreventive agents against breast carcinogenesis. This study examined the potential suppressive effect of the flavonoid on phorbol 12-myristate 13-acetate (PMA)-induced COX-2 expression in the non-tumorigenic MCF-10A and cancerous MCF-7 breast cells. Immunoblot and mRNA analyses revealed that butein at or below 10 μM significantly inhibited PMA-induced COX-2 expression in these breast cells. The blocking of the PKC signaling pathway appeared to be the underlying mechanism. Butein treatment reduced the amount of phospho-mitogen activated protein kinase (MAPK) ERK-1/2, and the total activity of PKC. Activated ERKs might trigger the transcriptional activation of COX-2. Reporter gene assays as well as electrophoretic mobility shift assays (EMSA) illustrated that butein inhibited transcription of this gene. This study showed that butein down-regulated PMA-induced COX-2 expression in both cancerous and non-cancerous breast cells, and such findings could provide the basis for pharmaceutical development of butein.
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Construction of a plant expression vector of chalcone synthase gene of Ginkgo biloba L. and its genetic transformation into tobacco. ACTA ACUST UNITED AC 2010. [DOI: 10.1007/s11703-010-1033-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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Song DG, Lee JY, Lee EH, Jung SH, Nho CW, Cha KH, Koo SY, Pan CH. Inhibitory effects of polyphenols isolated from Rhus verniciflua on Aldo-keto reductase family 1 B10. BMB Rep 2010; 43:268-72. [DOI: 10.5483/bmbrep.2010.43.4.268] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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Lee SK, Jung HS, Eo WK, Lee SY, Kim SH, Shim BS. Rhus verniciflua Stokes extract as a potential option for treatment of metastatic renal cell carcinoma: report of two cases. Ann Oncol 2010; 21:1383-1385. [PMID: 20363807 DOI: 10.1093/annonc/mdq154] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Affiliation(s)
- S K Lee
- Mμ Integrative Cancer Center, East West Neo Medical Center, Kyung Hee University, Seoul, Korea.
| | - H S Jung
- Mμ Integrative Cancer Center, East West Neo Medical Center, Kyung Hee University, Seoul, Korea
| | - W K Eo
- Mμ Integrative Cancer Center, East West Neo Medical Center, Kyung Hee University, Seoul, Korea
| | - S Y Lee
- Appalachian College of Pharmacy, Oakwood, VA, USA
| | - S H Kim
- Graduate School of East West Medical Science
| | - B S Shim
- College of Oriental Medicine, Kyung Hee University, Seoul, Korea
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Lee SH, Choi WC, Kim KS, Park JW, Lee SH, Yoon SW. Shrinkage of Gastric Cancer in an Elderly Patient Who Received Rhus verniciflua Stokes Extract. J Altern Complement Med 2010; 16:497-500. [PMID: 20423218 DOI: 10.1089/acm.2008.0237] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Affiliation(s)
- Sang-Hun Lee
- Department of Internal Medicine, Mu Integrative Cancer Center, East–West Neo Medical Center, College of Oriental Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Won-Cheol Choi
- Department of Clinical Oncology, Mu Integrative Cancer Center, East–West Neo Medical Center, College of Oriental Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Kyung-Suk Kim
- Department of Internal Medicine, Mu Integrative Cancer Center, East–West Neo Medical Center, College of Oriental Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Jae-Woo Park
- Department of Internal Medicine, Mu Integrative Cancer Center, East–West Neo Medical Center, College of Oriental Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Sang-Hoon Lee
- Department of Acupuncture and Moxibustion, Mu Integrative Cancer Center, East–West Neo Medical Center, College of Oriental Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Seong-Woo Yoon
- Department of Internal Medicine, Mu Integrative Cancer Center, East–West Neo Medical Center, College of Oriental Medicine, Kyung Hee University, Seoul, Republic of Korea
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Lee SH, Choi WC, Yoon SW. Impact of standardized Rhus verniciflua stokes extract as complementary therapy on metastatic colorectal cancer: a Korean single-center experience. Integr Cancer Ther 2009; 8:148-52. [PMID: 19679623 DOI: 10.1177/1534735409336438] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND To investigate the clinical feasibility of the standardized Rhus verniciflua Stokes (RVS) extract for the metastatic colorectal cancer (mCRC), experimentally proven to have anticancer activities. PATIENTS AND METHODS From July 2006 to November 2007, patients with conventional chemotherapy refractory mCRC were checked. After fulfilling inclusion/exclusion criteria, 36 patients were eligible for the final analysis. Overall survival and adverse events of patients treated with RVS in the aftercare period were determined. RESULTS On October 21, 2008, a total of 26 patients died while the remaining 10 patients were alive with evidence of disease. The median RVS administration period was 2.7 months (95% confidence interval, 1.9-3.5). The median overall survival for the entire population was 10.9 months (95% confidence interval, 5.6-16.1) and 1-year survival rate was 44.4%, which is compatible with external controls. By survival analysis using Cox proportional hazards model, the performance status and the prior chemotherapy regimen number significantly affected overall survival. Adverse reactions to the RVS treatment were mostly mild and self-limiting. CONCLUSION Complementary treatment with the standardized RVS extract might be beneficial for patients with mCRC, since it positively affected overall survival without significant side effects. This study suggests that RVS could be a natural anticancer agent candidate for the treatment of colorectal adenocarcinoma.
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Affiliation(s)
- Sang-hun Lee
- Department of Clinical Oncology, College of Oriental Medicine, M.mu Integrative Cancer Center, East-West Neo Medical Center Kyung Hee University, Seoul, Republic of Korea
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Kim JH, Jung CH, Jang BH, Go HY, Park JH, Choi YK, Hong SI, Shin YC, Ko SG. Selective cytotoxic effects on human cancer cell lines of phenolic-rich ethyl-acetate fraction from Rhus verniciflua Stokes. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2009; 37:609-20. [PMID: 19606519 DOI: 10.1142/s0192415x09007090] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Rhus verniciflua Stokes (RVS) is a plant with a long history of medicinal use in Eastern Asia. RVS has been widely used to treat gastritis, stomach cancer and atherosclerosis. The cytotoxic effects of different solvent fractions from an RVS ethanol extract were measured in 11 human cancer cell lines. The study showed that the ethyl-acetate (EtOAC) fraction was the most cytotoxic. This fraction contains a number of phenolic compounds, and this phenolic-rich EtOAC fraction was particularly effective against gastric and breast cancer cells. A purified phenolic-rich EtOAC fraction (PPEF) had a stronger apoptotic effect on these cells. Liquid chromatography-mass spectrometry (LC-MS) analysis showed that the PPEF contained gallic acid, protocatechuic acid, fisetin, sulfuretin, butein and 8 unknown compounds. There were only small amounts of flavonoids: fisetin, sulfuretin and butein. The results showed that PPEF induces apoptosis only in gastric and breast cancer cell lines, but not in lung, colon or liver cancer cell lines. Therefore, PPEF may have a significant potential as an organ-specific anti-cancer agent.
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Affiliation(s)
- Ji Hye Kim
- Department of Basic Science of Oriental Medicine, Kyunghee University, Seoul 130-701, Republic of Korea
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Lee JH, Lee HJ, Lee HJ, Choi WC, Yoon SW, Ko SG, Ahn KS, Choi SH, Ahn KS, Lieske JC, Kim SH. Rhus verniciflua Stokes prevents cisplatin-induced cytotoxicity and reactive oxygen species production in MDCK-I renal cells and intact mice. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2009; 16:188-197. [PMID: 19150236 DOI: 10.1016/j.phymed.2008.10.009] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/21/2008] [Revised: 09/30/2008] [Accepted: 10/23/2008] [Indexed: 05/27/2023]
Abstract
Cisplatin-induced oxidative stress can cause liver and kidney damage, thus limiting therapeutic efficacy. Thus, in the present study, since Rhus verniciflua Stokes (RVS) containing flavonoids has antioxidant effects, we investigated whether it can protect cisplatin-induced toxicity in vitro and in vivo, The in vitro effects of RVS on the cell viability and reactive oxygen species (ROS) production were investigated using cisplatin-treated Madin-Darby Canine kidney (MDCK)-I renal cells. Its in vivo effects were also studied in BALB/c mice inoculated with CT-26 colon adenocarcinoma cells and treated with cisplatin with or without RVS. Liver and renal functions were assessed together with indices of tissue oxidation. RVS prevented cisplatin-induced cytotoxicity and ROS release against MDCK-I cells. RVS alone exerted modest antitumor activity against CT-26 cells. When used concurrently with cisplatin, RVS prevented the increases in serum blood urea nitrogen (BUN), creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and NO, while reducing liver and kidney tissue MDA content, and increasing catalase, glutathione (GSH), and superoxide dismutase (SOD) activities. Moreover, the antitumor efficacy of cisplatin was not altered by concurrent administration of RVS. These findings demonstrate that RVS prevents cisplatin-induced toxicity in vitro and in vivo via an antioxidant activity without hurting its antitumor effectiveness, suggesting that RVS can be usefully applied to the neoplastic patients as a combined chemopreventive agent with cisplatin.
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Affiliation(s)
- Joo-Ho Lee
- College of Oriental Medicine, Cancer Preventive Material Development Research Center, Kyunghee University, 1 Hoegi-Dong Dongdaemun-Gu, Seoul 130-701, Republic of Korea
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Lee EH, Song DG, Lee JY, Pan CH, Um BH, Jung SH. Inhibitory effect of the compounds isolated from Rhus verniciflua on aldose reductase and advanced glycation endproducts. Biol Pharm Bull 2008; 31:1626-30. [PMID: 18670102 DOI: 10.1248/bpb.31.1626] [Citation(s) in RCA: 64] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
The aim of this paper was to evaluate active principles for diabetic complications from Rhus verniciflua. Nine compounds were isolated via bioactivity guided fractionation and isolation and tested for their effects on recombinant human aldose reductase and advanced glycation endproducts. Butein and sulfuretin isolated from ethyl acetate fraction were found to possess strongly both forms of aldose reductase and advanced glycation endproducts inhibition. The inhibitory activity of butein against a recombinant human aldose reductase (IC(50) value: 0.5 microM) was 2.6 times more potent that of epalrestat as a positive control (IC(50) value: 1.3 microM). The inhibitory potency of sulfuretin (IC(50) value: 124.7 microM) on advanced glycation end-products was about 10 times more potent that of aminoguanidine as a positive control (IC(50) value: 1231.0 microM). These compounds all displayed antioxidative activity which was measured by Photochem apparatus. It was concluded, therefore, butein and sulfuretin have antioxidative as well as aldose reductase and advanced glycation endproducts inhibitory effects. As a result, these compounds could be proposed as a leading compound for further study as a new natural products drug that could be used for diabetic complications.
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Affiliation(s)
- Eun Ha Lee
- Natural Products Research Center, Korea Institute of Science and Technology (KIST) Gangneung Institute, Gangneung, Korea
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