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Combined effect of vitamin D3 analogs and paclitaxel on the growth of MCF-7 breast cancer cells in vivo

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Abstract

Vitamin D3 analogs and paclitaxel (Taxol) are able to inhibit the in vitro growth of a variety of malignant cells including breast cancer cells. These two compounds decrease growth by different mechanisms and they have non-overlapping toxicities. We examined the abilities of three vitamin D3 compounds to inhibit growth of a human mammary cancer (MCF-7) in BNX triple immunodeficient mice either alone or with Taxol. Vitamin D3 analogs were 1,25(OH)2D3 (code name, Compound C), 1,25(OH)2-16-ene-23-yne-19-n or-26,27-F6-D3 (Compound LH), and 24a,26a,27a,-trihomo-22,24-diene-1,25(OH)2D3 (EB1089). At the doses chosen, the antitumor effect of vitamin D3 analogs alone was greater than that of Taxol alone, and an additive effect was observed when a vitamin D3 analog and Taxol were administered together. EB1089 was the most potent compound, and the EB1089 plus Taxol was the most active combination, decreasing the tumor mass nearly 4-fold compared to controls. Weight-gain in each of the experimental cohorts at the end of the study was less than the control group, but the gain was significantly less in only two experimental groups (those receiving either EB1089 or Compound C plus Taxol). None of the animals became hypercalcemic, and their complete blood counts, serum electrolyte analyses, and liver and renal functions were all fairly similar and within the normal range. In summary, this combination of a vitamin D3 analog and Taxol has the potential to be a therapy for breast cancer.

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Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Medicine, UCLA School of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Kozo Koshizuka, Michiaki Koike, Hiroya Asou, Steve K. Cho & H. Phillip Koeffler

  2. Orthopedic Hospital, Los Angeles, CA, USA

    Tony Stephen & Robert K. Rude

  3. Department of Biology, Leo Pharmaceutical Products, Ballerup, Denmark

    Lise Binderup

  4. Hoffman-LaRoche, Nutley, NJ, USA

    Milan Uskokovic

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  1. Kozo Koshizuka
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  2. Michiaki Koike
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  3. Hiroya Asou
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  4. Steve K. Cho
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  7. Lise Binderup
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  8. Milan Uskokovic
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  9. H. Phillip Koeffler
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Koshizuka, K., Koike, M., Asou, H. et al. Combined effect of vitamin D3 analogs and paclitaxel on the growth of MCF-7 breast cancer cells in vivo. Breast Cancer Res Treat 53, 113–120 (1999). https://doi.org/10.1023/A:1006123819675

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