Seocalcitol (EB1089) Description:IC50: In SKHEP-1 cells, the IC50 for seocalcitol was 460.99 nM. Calcitriol receptor, also known as the vitamin D receptor (VDR), is a member of the nuclear receptor family of transcription factors. The VDR not only regulates transcriptional responses but also involved in microRNA-directed post transcriptional mechanisms. Seocalcitol (EB1089) is a vitamin D analog that has been extensively studied and shown to have profoundly reduced hypercalcemic effects. In vitro: In a previous in vitro study, it was found that proliferation of Hep 3B, PLC/PRF/5 and SKHEP-1 HCC cells was significantly inhibited at all seocalcitol concentrations tested, while HTC cells only responded to 1,000 nM concentration of EB1089. However, proliferation of Novikoff cells was unaffected by the drug at all concentrations examined [1]. Another cell in-vitro study indicated that EB1089 significantly inhibited HEp-2 cell proliferation and increased p57 mRNA and protein levels; this was blocked by siRNA-p57 but not by siRNA-con [2]. In vivo: Seocalcitol effectively inhibited SKHEP-1 tumor growth without inducing hypercalcemia (p<0.05). These results indicate that seocalcitol is an effective growth inhibitor of HCC tumors [1]. Clinical trial: 56 patients with inoperable advanced HCC were included in an uncontrolled study of oral Seocalcitol treatment for up to 1 year. Out of 33 patients evaluable for tumour response, two had complete response (CR), 12 stable disease and 19 progressive disease. The CRs appeared after 6 and 24 months of treatment, and lasted for 29 and at least 36 months. Seocalcitol was well tolerated; the most frequent toxicity was hypercalcaemia and related symptoms. Most patients tolerated a daily dose of 10 mg of Seocalcitol. These data showed that Seocalcitol may have an effect in the treatment of HCC, especially in early disease when a prolonged treatment can be instituted. The survival benefit with or without tumour response should be determined in controlled studies [3]. Reference: [1] Ghous Z, Akhter J, Pourgholami MH, Morris DL. Inhibition of hepatocellular cancer by EB1089: in vitro and in vive study. Anticancer Res. 2008;28(6A):3757-61. [2] Lu L, Qiu J, Liu S, Luo W. Vitamin D3 analogue EB1089 inhibits the proliferation of human laryngeal squamous carcinoma cells via p57. Mol Cancer Ther. 2008;7(5):1268-74. [3] Dalhoff K1 Dancey J, Astrup L, Skovsgaard T, Hamberg KJ, Lofts FJ, Rosmorduc O, Erlinger S, Bach Hansen J, Steward WP, Skov T, Burcharth F, Evans TR. A phase II study of the vitamin D analogue Seocalcitol in patients with inoperable hepatocellular carcinoma. Br J Cancer. 2003 21;89(2):252-7.
