Changes in the tumorigenic and metastatic properties of tumor cells treated with quercetin or 5‐azacytidine

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Abstract
The effect of quercetin, a flavonoid derivative, on the transplantability (tumorigenicity) and metastatic behavior of mouse tumor cells was studied. BMT‐11 cl‐9 fibrosarcoma cells were treated in vitro with quercetin, and after cloning by limiting dilution, cell suspensions of each clone were injected subcuta‐neously (s.c.) into syngeneic C57BL/6 mice at a dose of 2 × 105 cells per mouse. Out of 17 clones examined, 8 were nontumorigenic in normal mice (“regressor” clones), whereas these clones were able to grow in immunosuppressed (600‐rad‐irradiated) mice. Furthermore, 1 out of 9 tumorigenic clones metastasized spontaneously to the lungs despite the very low metastatic potential of the parent BMT‐11 cl‐9 cells. In contrast, all 15 clones selected from the untreated parental line grew progressively in normal mice with no evidence of metastases. The appearance of both regressor and metastatic clones was also observed after treatment with a DNA hypomethylating agent, 5‐azacytidine. These altered phenotypes resulting from treatment with both chemicals, however, were not necessarily stable if maintained in culture for several months. The data suggest that quercetin may be a useful new material for obtaining regressor or metastatic clones from parental tumor lines.