Cytotoxic mechanism of novel compound jiangxienone from Cordyceps jiangxiensis against cancer cells involving DNA damage response pathway |
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| Affiliation: | 1. Department of Surgery, Division of Pediatric Surgery, University of Manitoba and Children''s Hospital Research Institute of Manitoba, Biology of Breathing Theme, Winnipeg, Manitoba, Canada;2. Department of Pediatrics & Child Health and Physiology & Pathophysiology (Adjunct), University of Manitoba and Children''s Hospital Research Institute of Manitoba, Biology of Breathing Theme, Winnipeg, Manitoba, Canada;3. Department of Pathology, University of Manitoba, and Shared Services Manitoba, Winnipeg, MB, Canada;4. Department of Pediatric Surgery, University Hospital Leipzig, Leipzig, Germany;1. Department of Pharmacology and Graduate Institute of Medical Sciences, School of Medicine, Taipei Medical University, Taipei, Taiwan;2. Department of Internal Medicine, School of Medicine, Taipei Medical University, Taipei, Taiwan;3. Core Facility Center, Office of Research and Development, Taipei Medical University, Taipei, Taiwan;4. Department of Microbiology, Institute of Ophthalmology, Joseph Eye Hospital, Tiruchirappalli, Tamil Nadu, India |
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| Abstract: | Jiangxienone is a novel compound recently purified from the traditional Chinese medicinal mushroom Cordyceps jiangxiensis and was reported to show potent cytotoxicity against cancer cells. However, its mechanism of action remains unclear. In this work, the underlying mechanism of jiangxienone against human gastric cancer cells HGC-27 was investigated using whole-genome microarray. The results demonstrated that jiangxienone significantly decreased cell population of various human cancer cell lines, while slightly inhibited the colony formation of stromal cells from murine marrow even at a high concentration. Differential gene expression profiling indicated that the cytotoxic action of jiangxienone against HGC-27 is closely related to the DNA damage response pathway, which was evident by the identification of 23 DNA damage response-associated genes, such as XRCC4/5/6, NBS1, RAD51, and BRCA1/2. By using gel retardation assays, UV absorption spectrometry and single-cell gel electrophoresis, it was found that jiangxienone could bind to DNA and inhibit cancer cell growth. The above results indicated that the cytotoxic mechanism of jiangxienone against cancer cells was involved in the DNA damage response pathway. The findings will be helpful to the development of useful cancer chemopreventive compounds from C. jiangxiensis. |
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