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Cytotoxic mechanism of novel compound jiangxienone from Cordyceps jiangxiensis against cancer cells involving DNA damage response pathway

Paper ID Volume ID Publish Year Pages File Format Full-Text
34718 45040 2014 9 PDF Available
Title
Cytotoxic mechanism of novel compound jiangxienone from Cordyceps jiangxiensis against cancer cells involving DNA damage response pathway
Abstract

•DNA damage response pathway of novel compound jiangxienone against cancer cells.•Jiangxienone exhibited selective toxicity against human gastric cancer cells.•Jiangxienone slightly inhibits the proliferation of hematopoietic cells.•It is useful to evaluate the potential of jiangxienone as a therapeutic agent.

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.

Keywords
Jiangxienone; Cordyceps jiangxiensis; Cytotoxic mechanism; Whole-genome microarray; DNA damage response pathwayIC50, half maximal inhibitory concentration; UV, ultraviolet; DNA, deoxyribonucleic acid; DDP, cisplatin; DMSO, dimethylsulfoxide; EDTA, ethylen
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Cytotoxic mechanism of novel compound jiangxienone from Cordyceps jiangxiensis against cancer cells involving DNA damage response pathway
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Publisher
Database: Elsevier - ScienceDirect
Journal: Process Biochemistry - Volume 49, Issue 4, April 2014, Pages 697–705
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us