1,25(OH)2D3 modulation of mammary tumor cell growth in vitro and in vivo

Abstract

The biological role of 1,25(OH)2D3 in controlling Ca++ homeostasis in the body has been identified and widely investigated for a long time. More recently its effect in regulating cell proliferation or differentiated activity was described in a variety of normal and malignant cells. The present study was carried out to investigate the different aspects and biological mechanisms of this activity and to determine if the use of 1,25(OH)2D3 in the treatment of breast cancer patients could be considered. It is found that 1,25(OH)2D3 reduces the proliferation of MCF-7 and BT-20 cells lines regardless of their sex steroid receptor status. This effect is related to the concentration, from 10(-12) M to 10(-8) M. Its amplitude is less in other cell lines, but it opposes the EGF-induced increase of proliferation. It is observed that the proliferation rate of MCF-7 and BT-20 cells is increased when these tumor cells are cocultured with fibroblasts derived from breast tumor biopsies and that 1,25(OH)2D3 reverses this process. Moreover, experiments on DMBA induced mammary tumors in Sprague Dawley rats found that 1,25(OH)2D3 given at non toxic doses reduces significantly the tumor proliferation. These data showed that 1,25(OH)2D3 at low doses is effective on the proliferation of BT-20 and MCF-7 cells and on the paracrine growth stimulatory effect observed in the presence of fibroblasts. They suggest that 1,25(OH)2D3 or related synthetic molecules which are less active on Ca++ metabolism could be useful in the treatment of breast cancer patients.

Plasma 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D and Risk of Breast Cancer

“…Numerous in vitro studies have indicated that 1,25(OH) 2 D can inhibit cell proliferation and promote cell differentiation in breast tumor tissue (5,(9)(10)(11), suggesting that high levels of vitamin D metabolites may be protective against breast cancer. In addition, several ecologic studies have reported lower breast cancer incidence and mortality rates in populations with high sunlight exposure, and thus higher vitamin D levels, compared with those with lower ambient sunlight (12)(13)(14)(15).…”

Vitamin D, Calcium, and Breast Cancer Risk: A Review

“…These observations, together with experimental evidence showing anticarcinogenic properties of vitamin D, have led to the hypothesis that high levels of vitamin D might reduce the risk of breast cancer (8)(9)(10)(11). In the United States, the main sources of dietary vitamin D intake are vitamin D -fortified dairy products, which are also rich sources of dietary calcium.…”

Plasma 25‐hydroxyvitamin D and premenopausal breast cancer risk in a German case‐control study

“…[1][2][3][4][5][6] Most of the epidemiologic studies regarding breast cancer risk have assessed the effects of vitamin D only for dietary intake yielding inconsistent results. [7][8][9][10][11][12][13][14][15] However, beside dietary intake, the main source of vitamin D is cutaneous production via sun exposure.…”