In contrast to cancer cells, most normal human cells have no or low telomerase 
levels which makes it an attractive target for anti-cancer drugs. The small 
molecule sulforaphane from broccoli is known for its cancer therapeutic 
potential in vitro and in vivo. In animals and humans it was found to be quickly 
metabolized into 4-methylthiobutyl isothiocyanate (MTBITC, erucin) which we 
recently identified as strong selective apoptosis inducer in hepatocellular 
carcinoma (HCC) cells. Here, we investigated the relevance of telomerase 
abrogation for cytotoxic efficacy of MTBITC against HCC. The drug was effective 
against telomerase, independent from TP53 and MTBITC also blocked telomerase in 
chemoresistant subpopulations. By using an orthotopic human liver cancer 
xenograft model, we give first evidence that MTBITC at 50 mg/KG b.w./d 
significantly decreased telomerase activity in vivo without affecting enzyme 
activity of adjacent normal tissue. Upon drug exposure, telomerase decrease was 
consistent with a dose-dependent switch to anti-survival, cell arrest and 
apoptosis in our in vitro HCC models. Blocking telomerase by the specific 
inhibitor TMPyP4 further sensitized cancer cells to MTBITC-mediated 
cytotoxicity. Overexpression of hTERT, but not enzyme activity deficient 
DNhTERT, protected against apoptosis; neither DNA damage nor cytostasis 
induction by MTBITC was prevented by hTERT overexpression. These findings imply 
that telomerase enzyme activity does not protect against MTBITC-induced DNA 
damage but impacts signalling processes upstream of apoptosis execution level.