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

• Published in: British journal of cancer Vol. 82; no. 2; pp. 452 - 458
• Main Authors: KOSHIUKA, K, ELSTNER, E, WILLIAMSON, E, SAID, J. W, TADA, Y, KOEFFLER, H. P
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 2000
• Subjects: Acids; Antineoplastic agents; Apoptosis; Arsenic; Biological and medical sciences; Breast cancer; Cancer research; Cancer therapies; Cell cycle; Chemotherapy; Disease; Drug dosages; Leukemia; Ligands; Medical prognosis; Medical research; Medical sciences; Pharmacology. Drug treatments; Prostate cancer; Radiation therapy; Regular; Remission (Medicine); Tumors; United States > US; Adenocarcinoma; Antineoplastic agent; Prostate disease; Retinoid; Arsenic compound; Cell cycle; Established cell line; Genetics; Mammary gland; Mechanism of action; Male genital diseases; Protooncogene; Organic compounds; Tretinoin; Human; Urinary system disease; Melarsoprol; Malignant tumor; In vitro; Mammary gland diseases; In vivo; Chemotherapy; Treatment; Cell death; C-Onc gene; Prostate; Apoptosis
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1054/bjoc.1999.0942

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 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 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.