[Chemical constituents of liquid culture of symbiotic Chaetomium globosum ML-4 of oyster and their in vitro antitumor activity].

Journal: Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica
PMID:

Abstract

Isolation and purification of chemical constituents of liquid culture of symbiotic Chaetomium globosum ML-4 of oyster was performed through silica gel column chromatography, gel filtration over Sephadex LH-20, preparative TLC and HPLC. Five compounds were obtained and their structures were determined as chaetoglobosin V(1), chaetoglobosin Vb(2), tyrosol(3), 5-methyluracil(4)and uracil(5), respectively, based on HR-MS and NMR data and comparison with literatures. In vitro cytotoxicity of compounds against human hepatocellular carcinoma cell line SMMC-7721 were measured byMTT method, and results showed that compound 1 could obviously inhibit the proliferation of SMMC-7721 cells with an IC₅₀ value of 60.5 mg•L⁻¹, while the IC₅₀ value of positive control cisplatin was 19.96 mg•L⁻¹. Further studies discovered that compound 1 could lead to G2 phase arrest in SMMC-7721 cells and induce SMMC-7721 cells apoptosis. The ratio of Bcl-2/Bax in SMMC-7721 cells was decreased. The expression of protein Caspases-3,-8,-9 was improved and the expression and phosphorylation level of Akt were reduced. Aforementioned results revealed that in vitro antitumor activity of compound 1 against SMMC-7721 cells were related to G2 phase cell cycle arrest and induced-apoptosis. The induced-apoptosis was involved in both the mitochondrial pathway and the death receptor pathway and connected with activity decline of PI3K/Akt signaling pathway.

Authors

  • Dan Wan
    Medical College, Yangzhou University, Yangzhou 225001, China.
  • Xi Chen
    Department of Critical care medicine, Shenzhen Hospital, Southern Medical University, Guangdong, Shenzhen, China.
  • Li Zhu
    Medical College, Yangzhou University, Yangzhou 225001, China.
  • Feng-Wu Wang
    College of Food Science and Engineering, Qingdao Agricultural University, Qingdao 266109, China.
  • Gui-Mei Kong
    Medical College, Yangzhou University, Yangzhou 225001, China.
  • Gui-Yun Cao
    Medical College, Yangzhou University, Yangzhou 225001, China.
  • Li Shen
    Department of Clinical Pharmacy, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.