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

K. Koshiuka, E. Elstner, E. Williamson, J. W. Said, Y. Tada, H. P. Koeffler

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

The organic arsenical known as melarsoprol (Mel-B) is used to treat African trypanosomiasis. Recently another arsenical, As2O3 was 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 DU145 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 x 10-9 M for MCF-7, 2 x 10-7 M for PC-3, 3 x 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.

Original languageEnglish (US)
Pages (from-to)452-458
Number of pages7
JournalBritish Journal of Cancer
Volume82
Issue number2
DOIs
StatePublished - 2000
Externally publishedYes

Keywords

  • Apoptosis
  • Breast cancer
  • Melarsoprol
  • Prostate cancer
  • Retinoid

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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