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Breast Cancer Res Treat 1999 Jan;53(2):113-20
Combined effect of vitamin D3 analogs and paclitaxel on the growth of MCF-7
breast cancer cells in vivo.
Koshizuka K, Koike M, Asou H, Cho SK, Stephen T, Rude RK, Binderup L,
Uskokovic M, Koeffler HP
Department of Medicine, UCLA School of Medicine, Cedars-Sinai Medical Center,
Los Angeles, CA 90048, USA.
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
nonoverlapping 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-nor-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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