Effect of retinoic acid and palm oil carotenoids on oestrone sulphatase and oestradiol-17β hydroxysteroid dehydrogenase activities in MCF-7 and MDA-MB-231 breast cancer cell lines

Abstract

Oestrogen is important in the development of breast cancer. Oestrogen receptor positive breast cancers are associated with a better prognosis than oestrogen‐receptor negative breast cancers since they are more responsive to hormonal treatment. Oestrone sulphate acts as a huge reservoir for oestrogens in the breast. It is converted to the potent oestrogen, oestradiol (E2) by the enzymes oestrone sulphatase and oestradiol‐17β hydroxysteroid dehydrogenase (E2DH). Retinoic acid and carotenoids have been shown to have chemopreventive activity against some cancers. The aim of our study was to determine and compare the effects of retinoic acid and palm oil carotenoids on growth of and oestrone sulphatase and E2DH activities in the oestrogen receptor positive, MCF‐7 and oestrogen receptor negative, MDA‐MB‐231 breast cancer cell lines. Retinoic acid and carotenoids inhibited MCF‐7 cell growth but had no effect on MDA‐MB‐231 cell growth. Both retinoic acid and carotenoids stimulated oestrone sulphatase activity in the MCF‐7 cell line. E1 to E2 conversion was inhibited by 10−7 M carotenoids but was stimulated at 10−6 M in the MCF‐7 cell line. Retinoic acid had no effect on E1 to E2 conversion at 10−7 M but stimulated E1 to E2 conversion at 10−6 M. Retinoic acid and carotenoids had no effect on E2 to E1 conversion in the MCF‐7 cell line. Retinoic acid stimulated E1 to E2 conversion in the MDA‐MB‐231 cell line but had no effect on oestrone sulphatase activity or E2 to E1 conversion in this cell line. Both oestrone sulphatase and E2DH activity were not affected by carotenoids in the MDA‐MB‐231 cell line. In conclusion, retinoic acid and carotenoids may prevent the development of hormone‐dependent breast cancers since they inhibit the growth of the MCF‐7 cell line. Int. J. Cancer 88:135–138, 2000. © 2000 Wiley‐Liss, Inc.

Differential effect of hormone therapy on E1S-sulfatase activity in non-malignant and cancerous breast cells in vitro

“…While we are to our knowledge the first to study STS activity in non-malignant human breast cells (basal and after treatment), basal STS activity in MCF-7 cells has been measured before [25,35,37,[38][39][40][41][42][43][44][45][46][47] revealing varying results which might be due to different assay protocols. For example, some authors used intact cells [25,37,38,[42][43][44][45][46][47][48][49][50][51], others cell homogenates [39,50]. Similarly, after having added the substrate 3 [14,22,[53][54][55], 5.8 lM in dysplastic human breast tissue [55], and 5.6-10.0 lM in MCF-7 cells [35,43,46].…”

“…Furthermore, some authors measured E1 [37,38,45], E2 [12, 20, 25, 37, 42-44, 46, 51, 56], or E1 + E2 [39,47-49, our assay], respectively, as being representative for STS activity. Substrate concentration also varies from being in the physiological [38,41] and supraphysiological range (our assay).…”

Egg–laying capacity is limited by carotenoid pigment availability in wild gulls Larus fuscus

“…One possible explanation is that supplemental carotenoids increased the synthesis and/or antioxidant protection of yolk precursors. Carotenoids and retinoic acid (a vitamin A metabolite, ultimately derived from pro-vitamin A carotenoids such as β-carotene) stimulate expression of oestrogenic enzymes, which have been shown to increase oestrogen production in vitro (Ng et al 2000;Hughes et al 2001). Oestrogen stimulates hepatic expression of the genes that code for synthesis of very low-density lipoprotein (VLDL) and vitellogenin, the main sources of yolk lipid and protein, respectively (Speake et al 1998).…”

Retinoid‐mediated stimulation of steroid sulfatase activity in myeloid leukemic cell lines requires RARα and RXR and involves the phosphoinositide 3‐kinase and ERK‐MAP kinase pathways

“…All‐ trans retinoic acid (ATRA) increased the expression of MRNA encoding steroid sulfatase in HL60 cells and this was associated with an increase in enzymatic activity [Hughes et al, 2001]. Retinoid‐mediated increases in steroid sulfatase activity have also been observed in MCF‐7 breast cancer cells [Ng et al, 2000], several colon cancer cell lines [Hughes et al, 2001], and some prostate cancer cell lines [Hughes and Brown, unpublished observations]. In HL60 cells, the increase in steroid sulfatase activity is a bone fide marker of retinoid‐stimulated granulocytic differentiation.…”