Positive Health Online

Abstract

SCHEMPP and colleagues, Department of Dermatology, University of Freiburg, Hauptstrasse 7, D-79104 Freiburg, Germany, schempp@haut.ukl.uni-freiburg.de, uncovered a hitherto unreported activity – inhibition of tumour cell growth – by hyperforin, a natural antibiotic derived from St. John's wort .

Background

Methodology

The researchers analysed the effects of hyperforin in a range of human and rat tumour cell lines in vivo and in vitro . Measures included IC50 values (concentrations required to inhibit tumour cell growth by 50 %) and indicators of apoptosis (programmed cell death ) such as the generation of apoptotic oligonucleosomes, typical DNA-laddering, increases in specific enzyme activities (caspase-9 and caspase-3) and apoptosis-specific morphological changes (e.g. damage to mitochondria).

Results

Hyperforin inhibited human and rat tumour cell growth, with IC50 values of 3-15 µM . Hyperforin caused dose-dependent generation of apoptotic oligonucleosomes, typical DNA-laddering and structural changes characteristic of apoptosis in tumour cells. In a breast cancer cell line (MT-450), hyperforin increased the activities of the enzymes caspase-9 and caspase-3 ; the caspase inhibitor zVAD.fmk inhibited the hyperforin-mediated apoptosis . In MT-450 cells, hyperforin also caused damage to mitochondria . By contrast, the cytotoxic drug paclitaxol did not induce loss of Deltapsi(m) or other indicators of mitochondrial damage. Hyperforin was also able to cause the release of cytochrome C from isolated mitochondria. Treating MT-450 cells with the caspase inhibitor zVAD.fmk did not prevent hyperforin-induced mitochondrial membrane permeabilization. These findings indicated that the mitochondrial permeabilization was a cause rather than the result of caspase activation. When hyperforin and paclitaxol were compared in vivo, they both inhibited the growth of MT-450 cells in rats to a similar extent ; hyperforin showed no signs of acute toxicity .

Conclusion

Hyperforin is capable of significantly inhibiting tumour cell growth via activation of a mitochondria-mediated apoptosis pathway . Hyperforin also showed low toxicity in vivo . Taken together with the natural abundance of this agent, the findings indicate hyperforin to be a promising anticancer agent that deserves further study.

References

Schempp CM et al. Inhibition of tumour cell growth by hyperforin, a novel anticancer drug from St. John's wort that acts by induction of apoptosis. Oncogene 21 (8): 1242-50. Feb 2002.

Comment

These results need to be followed up.