Sinensetin isolated from Orthosiphon aristatus inhibits cell proliferation and induces apoptosis in hepatocellular carcinoma cells |
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| Institution: | 1. Centre for Advanced Studies in Botany, University of Madras, Guindy Campus, Chennai 600 025, Tamil Nadu, India;2. School of Life Sciences, B.S. Abdur Rahman Crescent Institute of Science and Technology, Vandalur, Chennai, 600 048, Tamil Nadu, India;3. Department of Endocrinology, University of Madras, Taramani Campus, Chennai, 600 113, Tamil Nadu, India;4. Department of Biochemistry, University of Madras, Guindy Campus, Chennai, 600 025, Tamil Nadu, India;1. Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran;2. Pharmaceutical Sciences Research Center, Shiraz University of Medical Science, Shiraz, Iran;3. Biotechnology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran;1. Key Laboratory for Green Chemical Technology of Ministry of Education, R&D Center for Petrochemical Technology, Tianjin University, Tianjin 300072, China;2. Collaborative Innovation Center of Chemical Science and Engineering, Tianjin 300072, China;1. State Key Laboratory of Bioreactor Engineering, Department of Food Science and Technology, School of Biotechnology, East China University of Science and Technology, Shanghai 200237, People’s Republic of China;2. Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, People’s Republic of China;3. Sports Health Center, Tongji University, Shanghai 200092, People’s Republic of China;4. Shanghai Collaborative Innovation Center for Biomanufacturing (SCICB), Shanghai 200237, People’s Republic of China;1. Institute for Research in Molecular Medicine (INFORMM), Universti Sains Malaysia, Penang, 11800, Malaysia;2. EMAN Testing and Research Laboratories, Department of Pharmacology, School of Pharmaceutical Sciences, Universti Sains Malaysia, Penang 11800, Malaysia;3. ACRF Department of Cancer Biology and Therapeutics, The John Curtin School of Medical Research, Australian National University, Australia;1. Laboratory of Biochemistry, College of Pharmaceutical Sciences, Matsuyama University, Matsuyama, Ehime, 790-8578, Japan;2. Department of Pharmacognosy, College of Pharmaceutical Sciences, Matsuyama University, Matsuyama, Ehime, 790-8578, Japan |
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| Abstract: | Orthosiphon aristatus is a traditional folk medicine extensively used in Southeast Asia because of its various pharmacological effects, including antioxidant, antitumor, and hypoglycemic activities. Orthosiphon extracts have been found to be cytotoxic to hepatocellular carcinoma (HCC) cells, which is attributed to their phytochemical content. However, the mechanism of action underlying the cytotoxic effects remains unclear. Hence, the present study investigated the effect of Sinensetin purified from O. aristatus on HCC in vitro. Sinensetin was isolated from O. aristatus leaves and the chemical structure was confirmed by ultra violet (UV)-vis, infrared (IR), nuclear magnetic resonance (NMR), and electrospray ionization mass spectrometry (ESI-MS). The results revealed that 24-h treatment with the purified compound markedly inhibited the survival of HepG2 cells, with IC50 of 39.93 ± 1.10 μg/mL. HepG2 cells treated with the IC50 of Sinensetin showed characteristic morphological changes, as determined by PI and AO/Etbr dual staining, including DNA fragmentation, thus confirming the apoptosis induction. Sinensetin induced cell cycle arrest at G0/G1 phase, and the data were substantiated by flow cytometry. Furthermore, Sinensetin modulated key signaling molecules; anti-apoptotic Bcl-xL was down-regulated, whereas the expressions of tumor suppressors TRAIL and PTEN were up-regulated. We conclude that Sinensetin can be effective against HCC. |
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| Keywords: | Sinensetin HepG2 cells DNA fragmentation Apoptosis Cell cycle analysis |
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