TY - JOUR
T1 - Long-term exposure of HL60 cells to 1,25-dihydroxyvitamin D3 reduces their tumorigenicity
T2 - A model for cancer chemoprevention
AU - Wang, Xuening
AU - Ponzio, Nicholas M.
AU - Studzinski, George P.
N1 - Funding Information: This work was supported by Grants 2 RO1-CA 44722 from the National Cancer Institute and 96-37-CCR-00 from the New Jersey State Commission on Cancer Research.
PY - 1997/9
Y1 - 1997/9
N2 - Several lines of evidence suggest that 1.25-dihydroxyvitamin D3 (1,25D3) may be important in chemoprevention of human cancer. Here, we show that human promyelocytic leukemia cells HL60 cultured in the presence of 30 nM 1,25D3 (30A cells) for 3 years exhibited a reduced rate of tumor growth when injected into nu/nu mice, while cells grown in 40 nM 1,25D3 (40AF cells) tailed to form detectable tumors in 11 out of the 12 inoculated mice. Interestingly, both 30A and 40AF cells grew approximately twice as fast as the parental HL60-G cells under tissue culture conditions, even in the presence of 1,25D3, to which they developed resistance. Testa of the susceptibility of these cells to natural killer (NK) cell cytotoxicity showed that 40AF, but not HL60-G or 30A cells, were targets for the murine spleen NK cells. However, lysis of 30A cells was also detected when human NK cells were used in this assay, though the effector-to-target cell ratio necessary to obtain significant lysis above background levels was higher for 30A (80:1) than for 40AF (10:1) cells. These results suggest a mechanism for the reported chemopreventive effects of sunlight-generated 1,25D3 or dietary vitamin D3.
AB - Several lines of evidence suggest that 1.25-dihydroxyvitamin D3 (1,25D3) may be important in chemoprevention of human cancer. Here, we show that human promyelocytic leukemia cells HL60 cultured in the presence of 30 nM 1,25D3 (30A cells) for 3 years exhibited a reduced rate of tumor growth when injected into nu/nu mice, while cells grown in 40 nM 1,25D3 (40AF cells) tailed to form detectable tumors in 11 out of the 12 inoculated mice. Interestingly, both 30A and 40AF cells grew approximately twice as fast as the parental HL60-G cells under tissue culture conditions, even in the presence of 1,25D3, to which they developed resistance. Testa of the susceptibility of these cells to natural killer (NK) cell cytotoxicity showed that 40AF, but not HL60-G or 30A cells, were targets for the murine spleen NK cells. However, lysis of 30A cells was also detected when human NK cells were used in this assay, though the effector-to-target cell ratio necessary to obtain significant lysis above background levels was higher for 30A (80:1) than for 40AF (10:1) cells. These results suggest a mechanism for the reported chemopreventive effects of sunlight-generated 1,25D3 or dietary vitamin D3.
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U2 - https://doi.org/10.3181/00379727-215-44150
DO - https://doi.org/10.3181/00379727-215-44150
M3 - Article
C2 - 9270724
SN - 0037-9727
VL - 215
SP - 399
EP - 404
JO - Proceedings of the Society for Experimental Biology and Medicine
JF - Proceedings of the Society for Experimental Biology and Medicine
IS - 4
ER -