Growth Inhibition by Retino! of a Human Breast Carcinoma Cell Line in Vitro and in Athymic Mice1

Although the anticarcinogenic and antiproliferative effects of vitamin A (retinol) have been extensively studied in vitro, there are few data regarding the response of human tumor cells to this agent in vivo. We have studied the effects of retinol on the human breast carcinoma cell line, MDA-MB-231. Initial in vitro studies on monolayer cultures demonstrated a retinol-induced growth inhibition that was reversible as well as time and dose dependent. A similar dose-dependent decrease in tumor cell growth was shown in vivo when BALB/c-nu/nu (athymic) mice were inoculated s.c. with MDA-MB-231 cells and given graded nontoxic doses of retinol intragastrically for 3 weeks. Tumor cells were also inhibited from lung colonization as "artificial" metastatic lesions when injected i.v. into athymic mice following retinol treatment. Spleen cells from these mice were assayed for natural killer cells as determined by their cytotoxic activity on 51Cr-labeled target cells. There was no change in natural killer activity with any dose of retinol. We conclude that retinol has a dose-depend ent antiproliferative effect on human breast carcinoma in vivo as well as in vitro. Further, the retinol-induced tumor inhibition seen in T-cell-deficient mice does not appear to be due to enhance ment of host immunity and thus may be solely a direct effect of retinol on the tumor.