NDLI: Novel therapeutic approach: organic arsenical (melarsoprol) alone or with all-trans -retinoic acid markedly inhibit growth of human breast and prostate cancer cells in vitro and in vivo

Content Provider	PubMed Central
Author	Koshiuka, K. Elstner, E. Williamson, E. Said, J. W. Tada, Y. Koeffler, H. P.
Copyright Year	2000
Abstract	The organic arsenical known as melarsoprol (Mel-B) is used to treat African trypanosomiasis. Recently, another arsenical, As2O3was shown to be effective in treatment of acute promyelocytic leukaemia. We have investigated the anti-tumour activities of Mel-B either with or without all-trans -retinoic acid (ATRA) using the MCF-7 human breast cancer cells, as well as the PC-3 and DU 145 human prostate cancer cells both in vitro and in vivo. The antiproliferative effects of Mel-B and/or ATRA against breast and prostate cancer were tested in vitro using clonogenic assays and in vivo in triple immunodeficient mice. Furthermore, the mechanism of action of these compounds was studied by examining the cell cycle, levels of bcl-2, apoptosis and antiproliferative potency using a pulse-exposure assay. Clonogenic assays showed that the cancer cell lines were sensitive to the inhibitory effect of Mel-B (effective dose that inhibited 50% clonal growth [ED50]: 7 × 10−9 M for MCF-7, 2 × 10−7 M for PC-3, 3 × 10−7 M for DU145 cells. Remarkably, the combination of Mel-B and ATRA had an enhanced antiproliferative activity against all three cancer cell lines. Furthermore, the combination of Mel-B and ATRA induced a high level of apoptosis in all three cell lines. Treatment of PC-3 and MCF-7 tumours growing in triple immunodeficient mice with Mel-B and ATRA either alone or in combination markedly retarded tumour size and weight of the tumours without major side-effects. In conclusion, our results suggest that either Mel-B alone or with ATRA may be a useful, novel therapy for breast and prostate cancers. © 2000 Cancer Research Campaign
Related Links	http://dx.doi.org/10.1054/bjoc.1999.0942
Ending Page	458
Page Count	7
Starting Page	452
File Format	PDF
ISSN	15321827
e-ISSN	15321827
Journal	British Journal of Cancer
Issue Number	2
Volume Number	82
Language	English
Publisher	Nature Publishing Group
Publisher Date	2000-01-01
Access Restriction	Open
Rights Holder	Nature Publishing Group
Subject Keyword	Cancer Research Oncology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

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