In-vitro free radical scavenging, antiproliferative and anti-zearalenone cytotoxic effects of 4-(methylthio)-3-butenyl isothiocyanate from Tunisian Raphanus sativus.
OBJECTIVE
The aim of this study was to investigate the antiradical and antioxidant properties of 4-(methylthio)-3-butenyl isothiocyanate (MTBITC) extracted from Raphanus sativus and to assess the effects of MTBITC on tumour cell growth, cytotoxicity induced by zearalenone, an oestrogenic mycotoxin, and modulation of the expression of the genes involved in these aspects of cell behaviour.


METHODS
A murine leukaemia cell line (L1210) was grown in vitro and supplemented with MTBITC (2, 4, 8, 16 and 32 microm) for 48 h. Cell growth was evaluated by the MTT assay. The chemopreventive role of MTBITC on the cytotoxic effect of zearalenone in a Balb/c mice keratinocyte cell line (C5-O) was also evaluated. Apoptosis and lipid peroxidation were assessed, as well as the expression of genes involved following zearalenone treatment alone or in combination with MTBITC.


RESULTS
MTBITC showed a significant ability to inhibit nitroblue tetrazolium reduction by superoxide radicals in a non-enzymatic superoxide generating system, to scavenge free radicals and to cause a decrease in L1210 cell growth. The C5-O cells treated with zearalenone alone showed a high frequency of apoptotic cells and lipid peroxidation, typical of oxidative stress generated by zearalenone. The cotreatment with MTBITC reduced the cytotoxicity of zearalenone and the subsequent gene expression analysis demonstrated that MTBITC decreased the expression of caspase 8, implicated in the physiological mechanism to eliminate injured or abnormal cells.


CONCLUSIONS
The results suggest that MTBITC was able to inhibit L1210 cell growth and counteract the zearalenone oxidative stress to C5-O cells through caspase 8 inhibition of apoptosis.
Salah-Abbès
Jalila Ben
JB
Laboratory of Immunology, Environmental Microbiology and Cancerology, Faculty of Sciences Bizerte, Zarzouna, Tunisia. jalila.bensalah@yahoo.fr
Abbès
Samir
S
Abdel-Wahhab
Mosaad A
MA
Oueslati
Ridha
R
D000818:Animals; D016587:Antimutagenic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001713:Biphenyl Compounds / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D016166:Free Radical Scavengers / Q000302:isolation & purification / Q000494:pharmacology*; D005609:Free Radicals / Q000737:chemistry; D015870:Gene Expression / Q000187:drug effects; D017879:Isothiocyanates / Q000302:isolation & purification / Q000494:pharmacology*; D015603:Keratinocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis; D010851:Picrates / Q000737:chemistry; D018517:Plant Roots / Q000737:chemistry; D031224:Raphanus / Q000737:chemistry*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013481:Superoxides / Q000037:antagonists & inhibitors; D014416:Tunisia; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors; D015025:Zearalenone / Q000633:toxicity*
C447639:4-(methylthio)-3-butenyl isothiocyanate; D016587:Antimutagenic Agents; D000972:Antineoplastic Agents, Phytogenic; D001713:Biphenyl Compounds; D016166:Free Radical Scavengers; D005609:Free Radicals; D017879:Isothiocyanates; D010851:Picrates; D013481:Superoxides; D015025:Zearalenone; C004931:1,1-diphenyl-2-picrylhydrazyl; D014969:Xanthine Oxidase