Genotoxic, cytostatic, antineoplastic and apoptotic effects of newly synthesized antitumour steroidal esters

 
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2009 (EN)
Genotoxic, cytostatic, antineoplastic and apoptotic effects of newly synthesized antitumour steroidal esters

Mourelatos, Dionysios
Mioglou-Kalouptsi, Eleftheria
Nikolaropoulos, Sotirios
Bakopoulou, A.
Lialiaris, Theodoros S.
Karapidaki, I.
Papageorgiou, Athanasios
Iakovidou-Kritsi, Zafeiroula

In this study, we have investigated the genotoxic, cytostatic, antineoplastic and apoptotic effects of three newly synthesized modified steroidal esters, having as alkylating agent p-NN-bis(2-chloroethyl) aminophenyl butyrate (CHL) or p-N,N-bis(2-chloroethyl) aminophenyl acetate (PHE) esterified with the steroidal nucleus modified in the B- and D-ring. The genotoxic and cytotoxic effects of the compounds were investigated both in vitro,in lymphocyte Cultures obtained from blood samples of healthy donors and in vivo, in ascites cells of P388 leukemia obtained from the peritoneal cavity of DBA/2 mice. Preparations were scored for sister-chromatid exchange (SCE) and proliferation-rate indices (PRI). The newly synthesized compounds were also Studied for antineoplastic activity against lymphocytic P388 and lymphoid L1210 leukemias in mice, by calculating the mean of the median survival of the drug-treated animals (T) versus the untreated control (C) (T/C%). The activity of caspase-2 and caspase-3, indicators of apoptosis, was assessed biochemically in primary Cultures of human lymphocytes. Our results show that the newly synthesized compounds caused severe genotoxic effects by significantly increasing the frequency of SCE and decreasing the PRI values in cultures of peripheral lymphocytes in vitro and in ascites cells of lymphocytic P388 leukemia in vivo. A significant correlation was also observed in both the in vitro and in vivo experiments: the higher the SCE frequency the lower the PRI value (r = -0.65, P < 0.001 and r = -0.99, P < 0.01, respectively). The measured antileukemic potency was statistically increased by all test compounds in both types Of tumours, while the activity of caspase-2 and caspase-3 showed a statistically significant increase after two periods of exposure.

Article / Άρθρο
info:eu-repo/semantics/article

Cell Proliferation
Leukemia P388
Mice, Inbred C57BL
Cells, Cultured
Antineoplastic Agents
Esters
Androsterone
Nitrogen Mustard Compounds
Azasteroids
Animals
Cytostatic Agents
Lymphocytes
Mutagenicity Tests
Survival Analysis
Sister Chromatid Exchange
Mice, Inbred DBA
Molecular Structure
Ascites
Leukemia L1210
Apoptosis
Drug Screening Assays, Antitumor
Steroids

Αριστοτέλειο Πανεπιστήμιο Θεσσαλονίκης (EL)
Aristotle University of Thessaloniki (EN)

2009
2009-07-17T11:32:10Z


Αριστοτέλειο Πανεπιστήμιο Θεσσαλονίκης, Σχολή Επιστημών Υγείας, Τμήμα Ιατρικής

Mutation Research -Genetic Toxicology and Environmental Mutagenesis, vol.675 no.1-2 [2009] p.51-59 [Published Version]
urn:ISSN:13835718

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