Hybrigenics' inecalcitol inhibits the growth of human hormone-dependent prostate cancer cells in vitro and in vivo

15-Jul-2011 - France

Hybrigenics announced the publication of a scientific article by Dr Ryoko Okamoto and co-authors in the peer-reviewed International Journal of Cancer. Their preclinical results demonstrate the potential of inecalcitol to inhibit the proliferation of human cancer cells in vitro, as well as the growth of hormone-dependent prostate cancer xenografts in vivo in mice. Dr Okamoto works in Prof Phillip Koeffler's Division of Hematology and Oncology at the Cedars-Sinai Medical Center of the UCLA School of Medicine.

The results showed that inecalcitol was 11 times more potent than calcitriol, the naturally active metabolite of vitamin D, in inhibiting the growth in vitro of the human hormone-dependent prostate cancer cell line named LNCaP. The results also showed that, in vivo, inecalcitol was 480 times less toxic than calcitriol in mice. Inecalcitol was administered at the dose of 1.3 mg/kg by intraperitoneal injection three times per week for 42 days to nude mice bearing LNCaP xenografts; tumor growth was reduced by half as a result of inecalcitol treatment.

Interestingly, some molecular markers of activity were particularly responsive to inecalcitol treatment: ETS transcription factor variant 1 (ETV1) and Pim-1 kinase were down-regulated, while cytochrome P24A1 (24-hydroxylase), the main enzyme involved in the inactivation of vitamin D, was up-regulated. In addition, the same 11-fold difference in in vitro potency between inecalcitol and calcitriol was confirmed on the human promyeloid leukemia HL-60 cell line. Moreover, inecalcitol was 14 times more potent on this HL-60 cell line than on the hormone-dependent prostate cancer LNCaP cell line.

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