Premium
B‐Sitosterol(SIT) enhances tamoxifen(TX) effectiveness on breast cancer cells by increased production of ceramide and its metabolites
Author(s) -
Awad Atif B,
Barta Stephanie L,
Fink Carol S,
Bradford Peter G
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a565
Subject(s) - ceramide , chemistry , cell growth , tamoxifen , cell culture , serine , sulforhodamine b , endocrinology , biochemistry , medicine , breast cancer , cancer , apoptosis , biology , enzyme , cytotoxicity , in vitro , genetics
The objective of the present study was to investigate the effect of SIT, a dietary phytosterol, on the growth of two breast cancer cell lines, MCF‐7 (ER +) and MDA‐MB‐231(ER ‐) treated with TX. Cells were grown in RPMI 1640 media supplemented with 0–16μM SIT and 0–1μM TX or in combination for 3d. Cell growth was assessed by the sulforhodamine B assay. Ceramide and its metabolites were quantified using serine radiolabeling followed by TLC. Microsomal serine palmitoyl transferase (SPT) activity was measured with [ 3 H]serine substrate. Glycosylated ceramides were examined in lipid extracts by TLC after [ 3 H]galactose labeling. Results showed that SIT (16μM) inhibited cell growth of MCF‐7 by 40% and MDA‐MB‐231 by 60%. Growth of MCF‐7, but not MDA‐MB‐231, was inhibited (20%) by 1μM TX. The combination of 16μM SIT/1μM TX treatment on growth was more effective than 1μM TX alone in both cell lines. SIT treatment increased ceramide and its metabolites in both lines. SIT (16μM) activated SPT by 360% in MDA‐MB‐231 compared to 29% in MCF‐7 cells. TX (1μM), in the presence or absence of SIT (16μM), inhibited the glycosylation of ceramide in both cell lines. It is concluded that dietary SIT supplementation may be beneficial for breast cancer patients receiving TX. Supported by the Peanut Institute.