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

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 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.

1,25-Dihydroxyvitamin D3 and a superagonistic analog in combination with paclitaxel or suberoylanilide hydroxamic acid have potent antiproliferative effects on anaplastic thyroid cancer

“…Stage IVC patients had a significant clinical benefit, but without improved survival [32]. In other studies, co-treatment with 1,25(OH) 2 D 3 and paclitaxel resulted in enhanced anti-tumor activity in models of prostate cancer and breast cancer [33,34]. A clinical pharmacokinetic study of the combination treatment even suggested attenuation of the 1,25(OH) 2 D 3 -induced-hypercalcemia in combination with paclitaxel [35].…”

Vitamin D in cancer chemoprevention

“…Conversely, at the higher dose, EB1089 determined tumor regression. In addition, on one hand, experimental evidence showed that the combination of EB1089 with cytotoxic agents and/or ionizing radiation resulted in additive antitumor effects on breast cancer tumor cells either in vitro or in vivo (Demasters et al, 2006;Koshizuka et al, 1999;Sundaram et al, 2003;Valrance et al, 2007). On the other hand, Oades et al (2002) showed that EB1089 also inhibited the growth of prostate adenocarcinoma in the Dunning prostate model and in athymic nude mice transplanted with LNCaP.…”

Vitamin D and cancer

“…showed at least additive effects. In an in vivo breast cancer mice model, for example, additive effects on tumor growth inhibition were observed when the 1,25(OH) 2 D analog EB1089 was combined with taxol [47]. The use of 1,25(OH) 2 D or its analogs in humans has yet been very limited.…”