Abstract 4684: Vitamin D may impair glucocorticoid cytotoxicity in acute lymphoblastic leukemia cells

Abstract

Abstract Vitamin D deficiency has been associated with increased incidence and mortality in several types of cancer. Vitamin D has been shown to be cytotoxic to cancer cells in vitro, and may act synergistically with chemotherapy to kill cancer cells. Although vitamin D deficiency is common in children with cancer, the clinical implications of this remain unclear. Since acute lymphoblastic leukemia (ALL) is the most common type of cancer in children and relapsed leukemia remains a major problem, the present study was designed to test our hypothesis that active Vitamin D (Calcitriol) would induce apoptosis in ALL cells and potentiate the effect of chemotherapy on ALL cells. We cultured several human ALL cell lines and primary human ALL cells with and without Calcitriol, and quantified survival using trypan blue exclusion. Contrary to our hypothesis, Calcitriol did not negatively affect the viability or impair proliferation in the human ALL cell lines RS4; 11, SD1, BV173, or RCH-ACV, or in primary human ALL cells US7 or TXL 2. We then tested whether Calcitriol would synergize with dexamethasone, a glucocorticoid used almost universally in the treatment of childhood ALL. Again, contrary to our hypothesis, we found that rather than augment dexamethasone-induced cytotoxicity, supraphysiological doses of Calcitriol protected RS4;11 cells from the cytotoxic effect of 72 hour exposure to 100 nM dexamethasone (dexamethasone alone: 10±5% of initially plated cells viable; dexamethasone plus 300 nM Calcitriol: 27±14% of initially plated cells viable, n=4, p=0.04). More physiological doses of Calcitriol (10nM) showed similar protection (12.5±5% vs 31.5±19% of initially plated cells were viable at 72 hrs, n=4, p=0.05). Preliminary flow cytometry using Annexin/7AAD suggests that Calcitriol decreases dexamethasone-induced apoptosis in RS4;11 cells (dexamethasone alone: 94% of cells in apoptosis; dexamethasone plus 100 nM Calcitriol: 75% of cells in apoptosis, n=1) In summary, the active form of vitamin D appears to protect ALL cells from dexamethasone. This finding could be important, since glucocorticoid sensitivity of ALL cells is highly predictive of outcome and likelihood of relapse. Our findings could have major health implications given the high prevalence of Vitamin D deficiency in children and adolescents worldwide. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4684. doi:10.1158/1538-7445.AM2011-4684