Cytotoxic activity of hirsutanone,a diarylheptanoid isolated from Alnus glutinosa leaves |
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| Institution: | 1. Department of Pharmacology, Faculty of Pharmacy, Sevilla University, 41012 Sevilla, Spain;2. Department of Pharmaceutical and Health Sciences, Faculty of Pharmacy, CEU San Pablo University, 28668 Madrid, Spain;3. Department of Chemistry and Biochemistry, Faculty of Pharmacy, CEU San Pablo University, 28668 Madrid, Spain;1. Natural Products Research Institute, Korea Institute of Science and Technology, Gangneung 25451, Republic of Korea;2. Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea;3. College of Pharmacy, Sookmyung Women''s University, Seoul 04310, Republic of Korea;1. Drug Delivery and Formulation, Drug Discovery Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada;2. Faculty of Engineering and Architectural Science, Ryerson University, Toronto, Ontario, Canada;3. Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada;1. University of Southampton, Primary Care and Population Sciences, Aldermoor Health Centre, Aldermoor Close, Southampton, Hampshire SO16 5ST, United Kingdom;2. University of Southampton, Mathematical Sciences, Highfield, Southampton, Hampshire SO17 1BJ, United Kingdom;1. Department of Clinical Nutrition, School of Nutrition and Food Science, Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran;2. Department of Epidemiology and Biostatistics, School of Health, Isfahan University of Medical Sciences, Isfahan, Iran;3. Gynecologist and fellowship of infertility assistant professor of OB & GYN of Isfahan University of Medical Sciences, Isfahan, Iran;1. School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China;2. Clinical Pharmacy (School of Integrative Pharmacy, Institute of Integrative Pharmaceutical Research), Guangdong Pharmaceutical University, Guangzhou 510006, China;3. Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Guangzhou 510006, China;1. Department of Acupuncture and Moxibustion, Shanghai Tianshan Hospital of Traditional Chinese Medicine, Shanghai 200051, China;2. Department of Medical Clinic, Shanghai Institute of Acupuncture-Moxibustion and Meridians, Shanghai 200030, China;3. The Third Clinical College of Zhejiang Chinese Medical University, Hangzhou 310005, China |
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| Abstract: | BackgroundThe low efficacy of cancer therapy for the treatment of patients with advanced disease makes the development of new anticancer agents necessary. Because natural products are a significant source of anticancer drugs, it is important to explore cytotoxic activity of novel compounds from natural origin.PurposeThe aim of this work is to evaluate the cytotoxic capacity of hirsutanone, a diarylheptanoid isolated from Alnus glutinosa leaves. Hirsutanone cytotoxic way of action was also studied.Material and methodsThe cytotoxic ability of Alnus glutinosa leaves ethyl acetate extract was studied over HeLa and PC-3 cell lines, with the MTT colorimetric assay. Hirsutanone was isolated from this extract using chromatographic methods, and its structure elucidated by spectroscopic analysis. HT-29 cell viability after hirsutanone treatment was determined using SRB assay. In order to understand hirsutanone way of action, cytotoxicity was evaluated adding the diarylheptanoid and antioxidants. DNA topoisomerase II (topo II) poison activity, was also evaluated using purified topo II and a supercoiled form of DNA that bears specific topo II recognition and binding region; topo II poisons stabilize normally transient DNA-topo II cleavage complexes, and lead an increased yield of linear form as a consequence of a lack of double-strand breaks rejoining.ResultsThe diarylheptanoid hirsutanone was isolated from Alnus glutinosa (L.) Gaertn. (Betulaceae) leaves extract that showed cytotoxic activity against PC-3 and HeLa cell lines. Hirsutanone showed cytotoxic activity against HT-29 human colon carcinoma cells. Pre-treatment with the antioxidants NAC (N-acetylcysteine) and MnTMPyP (Mn(III)tetrakis-(1-methyl-4-pyridyl)porthyrin) reduced this activity, suggesting that reactive oxygen species (ROS) participate in hirsutanone-induced cancer cell death. Using human topo II and a DNA supercoiled form, hirsutanone was found to stabilize topo II-DNA cleavage complexes, acting as a topo II poison.ConclusionOur data suggest that, like curcumin, an induction of oxidative stress and topo II-mediated DNA damage may play a role in hirsutanone-induced cancer cell death. Since both compounds share similar structure and cytotoxic profile, and curcumin is in clinical trials for the treatment of cancer, our results warrant further studies to evaluate the anticancer potential of hirsutanone. |
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| Keywords: | Diarylheptanoid Cytotoxicity Hirsutanone Topoisomerase II Reactive oxygen species |
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