Efficient Accumulation and In Vitro Antitumor Activities of Triterpene Acids from Submerged Batch-Cultured Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Agaricomycetes)

2017 ◽  
Vol 19 (5) ◽  
pp. 419-431 ◽  
Author(s):  
Xiao-Ling Wang ◽  
Zhong-Yang Ding ◽  
Yan Zhao ◽  
Gao-Qiang Liu ◽  
Guo-Ying Zhou
Author(s):  
Mandy M Liu ◽  
Tiantian Liu ◽  
Steven Yeung ◽  
Zhijun Wang ◽  
Bradley Andresen ◽  
...  

Abstract The medicinal mushroom Ganoderma lucidum (GL, Reishi or Lingzhi) exhibits inhibitive effect on cancers. However, the underline mechanism of the antitumor activity of GL is still not fully understood. In this study, we characterized the gene networks regulated by a commercial product of GL containing mixture of spore and fruiting body, namely “GLSF”, in colorectal carcinoma. We found that, in vitro co-administration of GLSF extract at non-toxic concentrations significantly potentiated growth inhibition and apoptosis induced by paclitaxel in CT26 and HCT-15 cells. GLSF inhibited NF-κB promoter activity in HEK-293 cells but did not affect the function of P-glycoprotein in K562/DOX cells. Furthermore, we found that when mice were fed with a modified diet containing GLSF for one month prior to the CT26 tumor cell inoculation, GLSF alone or combined with Nab-paclitaxel markedly suppressed tumor growth and induced apoptosis. RNA-seq analysis of tumor tissues derived from GLSF-treated mice identified 53 differentially expressed genes compared to normal tissues. Many of GLSF-downregulated genes were involved in NF-κB-regulated inflammation pathways, such as IL-1β, IL-11 and Cox-2. Pathway enrichment analysis suggested several inflammatory pathways involving leukocyte migration and adhesion were most affected by the treatment. Upstream analysis predicted activation of multiple tumor suppressors such as α-catenin and TP53 and inhibition of critical inflammatory mediators. “Cancer” was the major significantly inhibited biological effect due to GLSF treatment. These results demonstrate that GLSF can improve the therapeutic outcome for colorectal cancer through a mechanism involving suppressing NF-κB-regulated inflammation and carcinogenesis.


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