Selenitetriglycerides-Redox-active agents

Pharmacol Rep. 2015 Feb;67(1):1-8. doi: 10.1016/j.pharep.2014.07.017. Epub 2014 Aug 14.

Abstract

Background: Human prostate cancer (hPCa) is the most commonly diagnosed cancer in elderly men and is the second leading cause of male cancer death. Data from epidemiological, eco-environmental, nutritional prevention and clinical trials suggest that selenium Se(IV) can prevent prostate cancer. Selol, a new organic semisynthetic derivative of Se(IV), is a mixture of selenitetriglycerides. This mixture is non-toxic and non-mutagenic, and after po treatment - 56-times less toxic (in mice) than sodium selenite. It exhibits strong anti-cancer activity in vitro in many cancer cell lines and can overcome the cell resistance to doxorubicin. Selol seems a promising compound for prostate cancer therapy.

Materials and methods: The aim of the present study is the evaluation of Selol's influence on intracellular redox state (Eh) of prostatic tumors and the liver in androgen-dependent hPCa-bearing mice, and extracellular redox state in serum of these mice.

Results and conclusions: The anticancer activity of Selol involves perturbation of the redox regulation in the androgen dependent hPCa (LNCaP) cells, but not in healthy cells. After Selol treatment, intracellular Eh has increased in tumors from -223 mV to -175 mV, while in serum it has decreased (-82 mV vs -113 mV). It shows significant changes Eh in the extra- and intracellular environment. The difference decreases from 141 mV to 62 mV. The changes suggest that a tumor cell was probably directed toward apoptosis. This is exemplified in a significant decrease in cancer tumor mass by approx. 17% after the three weeks of Selol administration.

Keywords: LNCaP; Oxidative stress; Redox state; Selenitetriglycerides; Selol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology*
  • Cysteine / metabolism
  • Cystine / metabolism
  • Extracellular Space / drug effects
  • Extracellular Space / metabolism
  • Humans
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Oxidation-Reduction
  • Oxidative Stress / drug effects
  • Prostatic Neoplasms / drug therapy
  • Selenium / analysis
  • Selenium / pharmacokinetics
  • Selenium Compounds / pharmacokinetics
  • Selenium Compounds / pharmacology*
  • Sulfhydryl Compounds / analysis
  • Tissue Distribution
  • Triglycerides / pharmacology

Substances

  • Antineoplastic Agents
  • Selenium Compounds
  • Sulfhydryl Compounds
  • Triglycerides
  • selol
  • Cystine
  • Selenium
  • Cysteine