[CANCER RESEARCH 61, 4294, May 15, 2001]
Letters to the Editor
Correspondence re: S. E. Blutt, T. C. Polek, L. V. Stewart, M. W. Kattan, and N. L. Weigel, A Calcitriol Analogue,
EB1089, Inhibits the Growth of LNCaP Tumors in Nude Mice. Cancer Res., 60: 779 –782, 2000.
Letter
We read with interest the report by Blutt et al. (1), demonstrating
inhibition of the growth of LNCaP prostate cancer cells in vivo by the
calcitriol analogue, EB1089. We reported previously significant in-
hibitory effects of EB1089 on the proliferation of prostate cancer cells
in vivo in the Dunning MAT LyLu prostate cancer model, a model of
androgen-insensitive, metastatic prostate cancer. In addition, we
showed that EB1089 significantly inhibits prostate cancer metastasis,
the primary cause of death in men with prostate cancer, and that this
effect can be achieved without inducing cachexia or unacceptable
levels of hypercalcemia (2). The report by Blutt et al. is consistent
with the hypothesis that vitamin D plays an important role in the
natural history of prostate cancer (3) and, with our findings that less
calcemic analogues of calcitriol, such as EB1089, hold promise as
therapeutic agents (4).
Gary G. Schwartz
Departments of Cancer Biology and Public Health Sciences
Comprehensive Cancer Center of Wake Forest University
Winston-Salem, North Carolina 27157
Bal L. Lokeshwar
Department of Urology
University of Miami School of Medicine
Miami, Florida 33101
Kerry L. Burnstein
Department of Molecular and Cellular Pharmacology
University of Miami School of Medicine
Miami, Florida 33101
References
1. Blutt, S. E., Polek, T. C., Stewart, L. V., Kattan, M. W., and Weigel, N. L. A calcitriol
analogue, EB1089, inhibits the growth of LNCaP tumors in nude mice. Cancer Res.,
60: 779 –782, 2000.
2. Lokeshwar, B. L., Schwartz, G. G., Selzer, M. G., Burnstein, K. L., Zhuang, S-H.,
Block, N. L., and Binderup, L. Inhibition of prostate cancer metastasis in vivo:a
comparison of 1,25-dihydroxyvitamin D (calcitriol) and EB1089. Cancer Epidemiol.
Biomark. Prev., 6: 241–248, 1999.
3. Schwartz, G. G., and Hulka, B. S. Is vitamin D deficiency a risk factor for prostate
cancer? Anticancer Res., 10: 1307–1311, 1990.
4. Schwartz, G. G., Oeler, T. A., Uskokovic, M. R., and Bahnson, R. R. Human prostate
cancer cells: inhibition of proliferation by vitamin D analogs. Anticancer Res., 14:
1077–1081, 1994.
Reply
Lokeshwar et al. (1) have made the interesting finding that
although the growth of MAT LyLu tumors was minimally affected
by EB1089 treatment, tumor metastasis to the lung was reduced.
Their finding that the MAT LyLu cells had undetectable levels of
functional vitamin D receptors suggests that there may be systemic
effects of EB1089 on tumor metastasis. However, the results of
these experiments should be interpreted with caution because the
EB1089 treatment caused a 19% elevation of serum calcium to a
clinically unacceptable level (12.7 mg/dl). Nonetheless, both the
Lokeshwar study (1) and our study (2) suggest that EB1089 or
other less calcemic analogues are promising candidates for the
treatment of prostate cancer.
Nancy L. Weigel
Sarah E. Blutt
Tara C. Polek
LaMonica V. Stewart
Department of Molecular and Cellular Biology
Baylor College of Medicine
Houston, Texas 77030
References
1. Lokeshwar, B. L., Schwartz, G. G., Selzer, M. G., Burnstein, K. L., Zhuang, S-H.,
Block, N. L., and Binderup, L. Inhibition of prostate cancer metastasis in vivo:a
comparison of 1,25-dihydroxyvitamin D (calcitriol) and EB1089. Cancer Epidemiol.
Biomark. Prev., 6: 241–248, 1999.
2. Blutt, S. E., Polek, T. C., Stewart, L. V., Kattan, M. W., and Weigel, N. L. A calcitriol
analogue, EB1089, inhibits the growth of LNCaP tumors in nude mice. Cancer Res.,
60: 779 –782, 2000. Received 3/6/00; accepted 3/16/01.
4294
Research.
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