1_WWW Selenitetriglycerides - Redox activ agents_2015-2

1_WWW Selenitetriglycerides - Redox activ agents_2015-2

Author's personal copy
Pharmacological Reports 67 (2015) 1–8
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Pharmacological Reports
j o u rn a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / p h a r e p
Original research article
Selenitetriglycerides—Redox-active agents
Anna Flis a, Piotr Suchocki a,c,* , Monika Anna Królikowska a, Zofia Suchocka b,
Małgorzata Remiszewska d, Lidia Śliwka a, Iza Ksia˛żek e, Karolina Sitarz e,
Małgorzata Sochacka a, Grażyna Hoser f, Elżbieta Anuszewska e, Piotr Wroczyński a,
Zenon Jastrze
˛ bski d
a
Department of Bioanalysis and Drugs Analysis,Medical Universityof Warsaw, Warszawa, Poland
Department of Biochemistry and Clinical Chemistry, Medical Universityof Warsaw, Warszawa, Poland
Department of Pharmaceutical Chemistry, National Medicines Institute, Warszawa, Poland
d
Department of Pharmacology, National Medicines Institute, Warszawa, Poland
e
Department of Biochemistry and Biofarmaceuticals, National Medicines Institute, Warszawa, Poland
f
The Center of Postgraduate Medical Education, Department of Clinical Cytology, Warsaw, Poland
b
c
AR T I C LE I N FO
AB S T R AC T
Article history:
Received 6 December 2013
Received in revised form 23 July 2014
Accepted 29 July 2014
Available online 14 August 2014
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 p.o. 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.
2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp.
z o.o. All rights reserved.
Keywords:
Selol
LNCaP
Selenitetriglycerides
Redox state
Oxidative stress
Introduction
Prostate cancer (PCa) is one of the most serious health and
social problems today. It is the most commonly diagnosed cancer
in elderly men and it is the second leading cause of male cancer
death [1,2] . More than 30% of early diagnosed cases do not survive
more than 5 years, and 20% of patients who undergo primary
treatment for prostate cancer still develop metastatic disease [3] .
Due to such alarming statistics, there is a constant need for new
* Corresponding author.
E-mail addresses: [email protected] , [email protected]
(P. Suchocki).
and effective drugs which could enhance the currently used forms
of therapy of the androgen-dependent prostate cancer, and/or
delay the recurrence of the lethal androgen-refractory form of the
disease. There is also a demand for drugs which reduce
chemoresistance of the androgen-insensitive form of hPCa. Data
from epidemiological, eco-environmental [4,5] , Nutritional Prevention of Cancer Trials [6,7] and clinical trials [8] suggest that
selenium (Se) may decrease the risk of some types of human
cancers and can prevent prostate cancer. It is well recognized that
dietary selenium is important for a healthy immune response [9] .
Selenium is an essential dietary component for humans and is
regarded as a cancer-preventive and cytoprotective agent in both
animal models and humans. Effects of Se supplementation depend
on the chemical form in which Se is provided. The organic form of
http://dx.doi.org/10.1016/j.pharep.2014.07.017
1734-1140/
2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.