Antineoplastic activities of MT81 and its structural analogue in Ehrlich ascites carcinoma-bearing Swiss Albino mice

Oxid Med Cell Longev. Jan-Feb 2010;3(1):61-70. doi: 10.4161/oxim.3.1.10495.

Abstract

Many fungal toxins exhibit in vitro and in vivo antineoplastic effects on various cancer cell types. Luteoskyrin,a hydroxyanthraquinone has been proved to be a potent inhibitor against Ehrlich ascites tumor cells. The comparative antitumor activity and antioxidant status of MT81 and its structural analogue [Acetic acid-MT81 (Aa-MT81)] having polyhydroxyanthraquinone structure were assessed against Ehrlich ascites carcinoma (EAC) tumor in mice. The in vitro cytotoxicity was measured by the viability of EAC cells after direct treatment of the said compounds. In in vivo study, MT81 and its structural analogue were administered (i.p.) at the two different doses (5, 7 mg MT81; 8.93, 11.48 mg Aa-MT81/kg body weight) for 7 days after 24 hrs. of tumor inoculation. The activities were assessed using mean survival time (MST), increased life span (ILS), tumor volume, viable tumor cell count, peritoneal cell count, protein percentage and hematological parameters. Antioxidant status was determined by malondialdehyde (MDA) and reduced glutathione (GSH) content, and by the activity of superoxide dismutase (SOD) and catalase (CAT). MT81 and its structural analogues increased the mean survival time, normal peritoneal cell count. They decreased the tumor volume, viable tumor cell count, hemoglobin percentage and packed cell volume. Differential counts of WBC, total counts of RBC & WBC that altered by EAC inoculation, were restored in a dose-dependent manner. Increased MDA and decreased GSH content and reduced activity of SOD, and catalase in EAC bearing mice were returned towards normal after the treatment of MT81 and its structural analogue. Being less toxic than parent toxin MT81, the structural analogue showed more prominent antineoplastic activities against EAC cells compared to MT81. At the same time, both compounds exhibit to some extent antioxidant potential for the EAC-bearing mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anthraquinones / pharmacology
  • Anthraquinones / therapeutic use*
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Ehrlich Tumor / drug therapy*
  • Carcinoma, Ehrlich Tumor / metabolism
  • Catalase / metabolism
  • Cells, Cultured
  • Glutathione / metabolism
  • Lipid Peroxidation / drug effects
  • Malondialdehyde / metabolism
  • Mice
  • Superoxide Dismutase / metabolism

Substances

  • Anthraquinones
  • Antineoplastic Agents
  • Malondialdehyde
  • MT81 mycotoxin
  • Catalase
  • Superoxide Dismutase
  • Glutathione