2. Academic Validation
  3. Mytoxin B and Myrothecine A Induce Apoptosis in Human Hepatocarcinoma Cell Line SMMC-7721 via PI3K/Akt Signaling Pathway

Mytoxin B and Myrothecine A Induce Apoptosis in Human Hepatocarcinoma Cell Line SMMC-7721 via PI3K/Akt Signaling Pathway

  • Molecules. 2019 Jun 20;24(12):2291. doi: 10.3390/molecules24122291.
Huiliang Song 1 2,  Yi Fu 3,  Dan Wan 4,  Wenjing Xia 5,  Fengwei Lyu 6,  Lijun Liu 7,  Li Shen 8 9 10
Affiliations

Affiliations

  • 1 Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou 225001, China. 18362825104@163.com.
  • 2 Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, Yangzhou 225001, China. 18362825104@163.com.
  • 3 School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, China. yfu@suda.edu.cn.
  • 4 Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou 225001, China. 18252717215@163.com.
  • 5 Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou 225001, China. wenjingxiajj@163.com.
  • 6 Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou 225001, China. yzdxyxyyx@163.com.
  • 7 Jiangsu Co-Innovation Center for Modern Production Technology of Grain Crops/Jiangsu Key Laboratory of Crop Genetics and Physiology, Yangzhou University, Yangzhou 225009, China. ljliu@yzu.edu.cn.
  • 8 Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou 225001, China. shenli@yzu.edu.cn.
  • 9 Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, Yangzhou 225001, China. shenli@yzu.edu.cn.
  • 10 Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China. shenli@yzu.edu.cn.
PMID: 31226773 DOI: 10.3390/molecules24122291
Abstract

Trichothecene macrolides comprise a class of valuable leading compounds in developing Anticancer drugs, however, there are few reports concerning their Anticancer mechanisms, especially the Anticancer mechanism of the 10,13-cyclotrichothecane derivatives that are found mainly in symbiotic fungi. In vitro Anticancer activity of two trichothecene macrolides mytoxin B and myrothecine A against the human hepatocarcinoma cell line SMMC-7721 was investigated in the present study. MTT assay showed that mytoxin B and myrothecine A inhibited the proliferation of SMMC-7721 cells in dose- and time-dependent manners. Annexin V-FITC/PI dual staining assay revealed that mytoxin B and myrothecine A both could induce SMMC-7721 cells Apoptosis in a dose-dependent manner. The decreased expression level of anti-apoptotic protein Bcl-2 and the increased expression level of pro-apoptotic protein Bax were observed apparently in Western blot analysis. The reduced ratio of Bcl-2/Bax further confirmed the apoptosis-inducing effect of mytoxin B and myrothecine A on SMMC-7721 cells. Moreover, the expression levels of caspases-3, -8, and -9, and cleaved caspases-3, -8, and -9 were all upregulated in both mytoxin B and myrothecine A-treated cells in Western blot analysis, which indicated that both compounds might induce SMMC-7721 cells Apoptosis through not only the death receptor pathway but also the mitochondrial pathway. Finally, mytoxin B and myrothecine A were found to reduce the activity of PI3K/Akt signaling pathway that was similar to the effect of LY294002 (a potent and specific PI3K Inhibitor), suggesting that both mytoxin B and myrothecine A might induce SMMC-7721 cells Apoptosis via PI3K/Akt pathway.

Keywords

PI3K/Akt signaling pathway; SMMC-7721 cells; anticancer mechanism; apoptosis; trichothecene macrolide.

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