Positive Health Online

Abstract

HAYON and colleagues, Department of Clinical Biochemistry, Faculty of Health Sciences, Soroka Medical Center, Beer Sheva, Israel studied the antitumour activity of non-steroidal antioestrogens, including Tamoxifen and its derivatives, in leukaemia and lymphoblastic cell lines .

Background

Methodology

The authors studied the effects of tamoxifen and its derivatives, clomiphene and nafoxidine in promyelocytic leukaemia HL60 and T lymphblastic MOLT3 cell lines.

Results

Tamoxifen and derivatives clomiphene and nafoxidine caused reduction of cell viability in a dose-dependent manner . The drugs demonstrated differences in the potency after four days incubation, with nafoxidine being the most efficient inhibitor and tamoxifen the least active . Apoptosis was induced, as measured by the DNA ladder pattern and formation of pre G0/G1 population detected by flow cytometry analysis of DNA. The drugs effect was counteracted by antioxidants, alpha-tocopherol (vitamin E) the most effective. N-acetyl L-cysteine reversed mainly decrease in cell viability, but was less effective upon apoptosis. The protein kinase inhibitor GF109203X attenuated apoptosis induced by clomiphene in MOLT3 cells.

Conclusion

These results suggest that the antileukaemic activity of these antioestrogens is mediated by oxidative stress and protein kinase C (PKC) activation. Tripheylethylene antioestrogens and their derivaties may be used as antileukaemic drugs which kill cells by apoptosis mediated by oxidative stress and activation of PKC.

References

Hayon T et al. Non-steroidal antiestrogens induce apoptosis in HL60 and MOLT3 leukemic cells; involvement of reactive oxygen radicals and protein kinase C. Anticancer Research 19(3A): 2089-93. May-Jun 1999.